UF Urology Urologic Cancers

The University of Florida Genitourinary Oncology program at Shands at UF provides a comprehensive approach to the diagnosis and treatment of patients with cancers of the prostate, bladder, kidney, adrenal gland, testis and penis. Patients referred to the UF GU Oncology program receive prompt evaluation and coordinated, compassionate cancer care by a multidisciplinary team of highly trained UF physician specialists and healthcare professionals from the departments of:

• Urology
• Radiation Oncology
• Medical Oncology
• Pathology
• Radiology
• Pharmacy
• Nursing
• Social Services
• Nutrition

All aspects of patient care, from the initial visit and evaluation through treatment, recovery and follow-up consultations, are coordinated by the UF GU Oncology nurse coordinator to guarantee patients receive the smoothest, most efficient and best care possible. Following a complete patient assessment and diagnostic evaluation, the multidisciplinary team collaborates to develop individualized patient treatment plans utilizing the latest in genetic profiling, minimally invasive surgery, radiotherapy and chemotherapy. This coordinated approach to patient care results in outstanding outcomes and improved quality of life for the patient. Advanced therapies and services utilized by the UF GU Oncology program include:

• Open, laparoscopic, robotic, nerve-sparing and salvage surgeries
• Total, focal and salvage cryosurgery
• Ablative therapy (radiofrequency ablation or cryosurgery)
• External Beam Radiotherapy
• Intensity Modulated Radiotherapy (IMRT) & Image Guided Radiotherapy (IGRT)
• Systemic therapy including chemotherapy and target therapy
• Access to clinical trials

To schedule an appointment or refer a patient to the UF Genitourinary Oncology center, call 352.265.8282.

Prostate cancer is the most common cancer diagnosed among American men, accounting for nearly 200,000 new cancer cases in the United States each year. Prostate cancer tends to occur most commonly in men over the age of 50, and greater than 65% of all cases are diagnosed in men 65 years and older. The incidence of prostate cancer increases with age; the lifetime risk for the average American man is about one-in-six, but only 8% of men develop prostate cancer between the ages of 50 and 70 years. Well-established risk factors include older age, family history, and race (African Americans are at greater risk). Other potential risk factors thought to be associated prostate cancer include a Western diet high in saturated fat and obesity.

The overwhelming majority of prostate cancers are adenocarcinomas, which arises from the glandular (acinar) component of the prostate. Other rare and atypical types of prostate cancer include:

Ductal carcinoma
Mucinous carcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Clear cell adenocarcinoma
Giant cell carcinoma

These rare and atypical variants often act aggressively and may respond differently to therapy than the more common prostate adenocarcinoma. As they are rare, however, most men are unaffected by these atypical variants.

The face of prostate cancer has changed significantly over the past 2 decades. Largely due to the widespread use of prostate specific antigen (PSA), most prostate cancers are now diagnosed at an earlier stage and younger age compared to 20 years ago. Although prostate cancer deaths have decreased in recent years, PSA screening continues to be controversial. While not endorsed universally, the American Cancer Society and American Urologic Association recommend prostate cancer screening beginning at age 50 for most men and at 40 years of age for African American men and those with a family history.

Local prostate cancer
Approximately 90% of prostate cancers are diagnosed at a localized stage (cancer confined to prostate without evidence of spread). Localized cancers are most commonly detected through an elevation in PSA without causing symptoms. Less commonly, prostate cancer may be detected by an abnormal digital rectal exam (DRE) or due to urinary symptoms, such as hematuria (blood in the urine) or problems with urination (difficulty or discomfort with urination). Not all local prostate cancers are the same. Some are indolent and will not cause problems while others are clinically significant and require treatment. Even among clinically significant cancers, there are differences that further separate cancers by risk (for example, low, intermediate and high risk prostate cancer). Factors that determine the risk and clinical significance of prostate cancer include PSA, Gleason grade and disease stage. There are several effective treatment options for men with clinically significant local prostate cancer, including surgery, external radiation therapy and interstitial brachytherapy. Treatment recommendations are usually made based on a number of factors, including disease characteristics, risk category, candidacy for a particular treatment, and patient preference. In some cases (low- and intermediate-risk prostate cancer, for example), a single treatment may be adequate for disease control. For others, particularly in high-risk prostate cancer, a combination of treatments may be required. For low-risk prostate cancer and among older men, active-surveillance (observation) is another management option. Although effective in cancer control, most prostate cancer treatments carry some risk of impacting urinary, sexual and bowel health. Newer treatment methods, however, continue to be developed to minimize the risks of these side effects (for example, nerve-sparing radical prostatectomy). Following treatment, approximately 15% to 25% of patients with early-stage (localized) prostate cancer experience a biochemical (PSA) recurrence, indicating possible need for additional therapy. However, the overall 5-year survival for patients with localized kidney cancer is close to 100%.

Advanced prostate cancer
Approximately 10% of prostate cancers are diagnosed at an advanced stage characterized by involvement of surrounding structures, spread to lymph nodes or metastasis to more distant sites. Advanced prostate cancer more commonly causes some symptoms, such as hematuria, urinary obstruction or bone pain. Treatment options for patients with metastatic prostate cancer are more limited, although in some settings, surgery or radiation therapy may still be indicated. More commonly, androgen deprivation therapy (ADT), also known as hormone therapy, is used to control metastatic disease and slow the growth of more advanced prostate cancers. Chemotherapy may also be used to manage patients with metastatic prostate cancer, although it is not a mainstay of management. Common sites of metastatic spread include the bone, liver and lungs. The overall 5-year survival for regionally advanced and metastatic prostate cancer is approximately 32%.

Signs & Symptoms
For most men, prostate cancer does not cause symptoms but is detected because of an elevation in prostate specific antigen (PSA). However, symptoms of the lower urinary tract, such as hematuria (blood in the urine), frequency (need to urinate frequently) and dysuria (discomfort or pain with urination) may be signs of prostate problems, including prostate cancer. Other uncommon symptoms of prostate cancer can include urinary retention, weight loss, abdominal pain, bone pain, or fracture.

Lower Urinary Tract Symptoms (Prostatism)
Frequency
Urgency
Hematuria (visible or microscopic)
Dysuria
Urinary retention

Pain Symptoms
Back pain
Pelvic pain
Bone pain

Constitutional symptoms
Weight loss

Diagnosis

Physical examination

PSA blood test

Prostate biopsy

Abdominal and pelvic CT scan

Bone scan (if indicated)

After taking a detailed medical history and performing a physical examination, including a digital rectal examination, a PSA blood test will be performed. If the PSA level is elevated, a prostate biopsy will be recommended. The biopsy is an outpatient procedure (you go home the same day) that is performed with local anesthesia. Several samples of tissue are obtained from the prostate. These samples are what tell us if you have prostate cancer. If the biopsy is positive, other tests may be performed based on your PSA level, cancer grade and findings on exam. Most commonly, a CT scan of the abdomen and pelvis will be obtained for clinical staging. In high-risk cases, a bone scan may be recommended to determine if there has been spread to the bones.

Staging for prostate cancer
Clinical staging is performed with Physical Examination and Abdominal and Pelvic CT scan. In cases of advanced or high-risk disease, additional testing such as Bone Scan may be necessary.

The prognosis of prostate cancer is directly linked to the stage of disease. Staging is a process that demonstrates how far the cancer has spread. Both treatment options and prognosis (or outlook) for prostate cancer depend significantly on the stage of disease.

TNM SYSTEM
Status
T0	No evidence of primary kidney tumor
T1	Clinically inapparent tumor not palpable or visable by imaging
T1a	Tumor incidental histologic finding in <5% of removed tissue
T1b	Tumor incidental histologic finding in >5% of removed tissue
T1c	Tumor identified by needle biopsy because of elevated PSA
T2	Tumor confined with the prostate
T2a	Tumor involves one-half of one lobe or less
T2b	Tumor involves > one-half of one lobe but not both lobes
T2c	Tumor involves both lobes
T3	Tumor extends through the prostate capsule
T3a	Extracapsular extension (unilateral or bilateral)
T3b	Tumor invades seminal vesicle(s)
T4	Tumor fixed or invades adjacent pelvic structures
N0	No regional lymph node metastasis
N1	Metastasis in regional lymph node or nodes
M0	No distant metastasis
M1	Distant metastasis
M1a	Metastasis to non-regional lymph node(s)
M1b	Metastasis to bone(s)
M1c	Metastasis to other site(s)

Treatment
Most prostate cancers are localized and can be treated with surgery, external radiation therapy or interstitial brachytherapy. In low-risk disease, observation or active surveillance may also be an option. Focal therapy using ablative technology is less common and is currently under investigation. Treatments for localized prostate cancer include:

Radical retropubic prostatectomy
Robotic-assisted laparoscopic prostatectomy
Radical perineal prostatectomy
3D-conformal radiation therapy
Intensity-modulated radiation therapy
Interstitial brachytherapy
Focal therapy
Active Surveillance (observation)

Radical retropubic prostatectomy (RRP) – consists of removal of the prostate gland and surrounding lymph nodes through an 8 cm open incision above the pubic bone. Radical retropubic prostatectomy is the most common open surgical approach to treating prostate cancer, and can be used to treat a range of prostate cancer, including low, intermediate and high-risk localized prostate cancer, as well as radiation refractory prostate cancer (termed salvage prostatectomy). Most patients spend 1-2 nights in the hospital and are sent home with a urinary (Foley) catheter, which stays in for a week following surgery to encourage healing of the urethra. Depending on the stage and risk of the disease, radical retropubic prostatectomy can be performed with nerve-sparing. Nerve-sparing prostatectomy provides the best chance of return of erections following surgery in men with good erectile function prior to treatment, and is typically used in low and intermediate-risk disease. In setting of high-risk disease, however, nerve-sparing may not be indicated as it may limit cancer control (removal of all cancer tissue). Like other types of surgical therapy, outcomes following radical retropubic prostatectomy (cancer control, urinary continence, erectile function and complications) tend to be better, on average, when performed by high-volume and fellowship-trained surgeons.

Robotic-assisted laparoscopic prostatectomy is one of the most common types of surgical treatments for prostate cancer, and its use in the management of localized prostate cancer has increased rapidly in recent years. The robotic approach takes advantage of the benefits of laparoscopy as well as small surgical working elements that replicate the movement of the human hand. In general, RALP is associated with less blood loss, a lower chance of requiring a blood transfusion, decreased pain post-operatively, and shorter convalescence. As with RRP, lymph nodes are removed with the prostate for pathologic staging. Patients tend to spend 1-2 nights in the hospital and are sent home with a urinary (Foley) catheter that stays in place for 7 to 10 days. As with open surgery, this procedure should be performed by a surgeon familiar with the robot and who is trained in performing radical prostatectomy. In general, high-volume (those surgeons who perform many procedures) and fellowship surgeons tend to have better outcomes than low-volume and non-fellowship-trained surgeons.

Radical perineal prostatectomy consists of removal of the prostate through an incision in the perineum (the area between the scrotum and anus), and was the first surgical approach used to treat prostate cancer. Today, perineal prostatectomy is relatively uncommon, but it is still used in certain cases, such as in obese patients in which access to the prostate from pelvis would be difficult. In intermediate and high-risk cases in which lymph node dissections are indicated, a separate lymph node dissection may be indicated to complete staging. Because it is an uncommon surgery, the surgeon should be familiar in this surgical approach.

3D conformal and Intensity-Modulated Radiation Therapy – Radiation therapy is an effective treatment for prostate cancer and can be used to manage low and high-risk cases. Currently, two types of external radiation therapy are used. 3D-conformal RT targets the prostate with the aid of imaging guiding to more accurately deliver radiation dose to the prostate with less radiation therapy exposure to surrounding tissues. Intensity-modulated RT uses more advanced technology to reduce dose to the areas of the bladder, rectum and bowel and boost dose to the prostate. For both modalities, a total radiation dose of 76 Gy should be administered and some studies have shown that higher doses are more effective. Radiation therapy is typically given in daily fractions over the course of 10 weeks. In intermediate- and high-risk prostate cancer, RT should be administered with ADT to maximize the treatment effect.

Interstitial prostate brachytherpay involves placement of small radioactive pellets, or “seeds” into the prostate. In general, this treatment can be used for small to normal sized prostates and for Gleason grade 6 or less tumors. In settings of higher risk disease (PSA>10 ng/mL or Gleason grade ³ 7) where there is concern for extraprostatic extension, external radiation therapy should be used in conjunction with interstitial bracytherapy to ensure adequate cancer control. In some cases, hormone therapy may be used before brachytherapy to help reduce the size of the prostate.

Active surveillance (observation) is used in some cases of low-risk disease, as well as among older patients for whom active treatment with surgery or radiation therapy may not be possible or necessary. Active surveillance is most often used because some prostate cancers may never become life threatening. PSA and DRE are typically checked periodically, and current active surveillance protocols recommend repeat biopsies to ensure that disease does not progress.

Focal therapy – ablative therapies such as cryoablation, radiofrequency ablation and high-frequency ultrasonic ablation are currently being studied as a way to limit treatment to the focal location of the cancer instead of treating the entire prostate with the hopes that focal therapy will be associated with fewer side effects than other non-focal treatments. Selection of appropriate, low-risk patients is essential because less therapy may not be adequate to control higher-volume or high-risk prostate cancer. Other concerns regarding focal therapy include targeting the tumor within the prostate accurately, identifying other areas of cancer within the prostate and offering more effective management compared to active surveillance.

Salvage therapy – In cases of prostate cancer recurrence following primary treatment, a secondary local therapy can lead to salvage and cure. Depending on which type of treatment was first used, salvage surgery, radiation therapy or cyro-abalation may be used to control recurrent disease.

Kidney cancer is the third most commonly occurring genitourinary cancer in adults. There are approximately 54,000 new cancer cases each year in the United States, and the incidence of kidney cancer appears to be on the rise. Kidney cancer tends to occur most commonly in individuals over the age of 40 and is more common in men than in women. Most kidney cancers occur spontaneously, although some are associated with hereditary conditions, including von Hippel-Lindau disease and hereditary papillary renal cell carcinoma. Potential risk factors include cigarette smoking, obesity and high blood pressure.

Although most growths that arise in the kidneys are cancers, about 20% to 25% of kidney tumors are benign. The most common types of benign kidney tumors are oncocytoma and angiomyolipoma. Renal cell carcinoma (RCC) is the most common type of kidney cancer. There are several sub-types of renal cell carcinoma. Clear cell (conventional) renal cell carcinoma is the most common sub-type and represents greater than 80% of renal cell carcinomas.

Other sub-types include:

Papillary renal cell carcinoma
Chromophobe renal cell carcinoma
Collecting duct renal cell carcinoma
Medullary renal cell carcinoma

Papillary and chromophobe variants of renal cell carcinoma are typically less aggressive than clear cell renal cell carcinoma. Collecting duct and medullary sub-types are very aggressive cancers characterized by relatively poor outcomes.

Local kidney cancer
Approximately 60% of kidney cancers are diagnosed at a localized stage (cancer confined to kidney without evidence of spread). Localized cancers may be detected incidentally without causing symptoms or may be associated with hematuria (blood in the urine), flank pain or abdominal discomfort. Surgery is the most effective treatment, although in some cases (very small tumors or in patients who are not suitable candidates for surgery) other ablative techniques are available. Following surgical treatment, approximately 20% to 30% of patients with localized kidney cancers relapse (develop recurrent disease). The overall 5-year survival for patients with localized kidney cancer is approximately 90%.

Advanced kidney cancer
Approximately 40% of kidney cancers are diagnosed at an advanced stage characterized by involvement of surrounding structures, spread to lymph nodes or metastasis to more distant sites. These tumors tend to be larger, and are more commonly high-grade and carry a higher risk of recurrence following treatment. Because chemotherapy and radiation are ineffective against kidney cancer, surgery still holds an important role in the management of advanced kidney cancer, and may even be recommended in the setting of metastatic disease. Common sites of metastatic spread include the lung, bone and brain. The overall 5-year survival for regionally advanced kidney cancer (spread to adjacent structures and lymph nodes) is approximately 60% but decreases to 10% for distant metastatic disease.

Signs & Symptoms

Hematuria
Visible
Microscopic

Abdominal or flank symptoms
Pain
Fullness or palpable mass

Constitutional symptoms
Fatigue
Weight loss
Fevers

Paraneoplastic syndromes
Hypertension (high blood pressure)
Hypercalcemia (high calcium level in blood)
Erythrocytosis (high blood counts)
Liver dysfunction (elevation in liver enzymes)

For many people, kidney cancer does not cause symptoms but is found incidentally on radiographic tests. In cases in which symptoms are present, the most common symptoms include hematuria (blood in the urine), abdominal discomfort or flank pain.

Diagnosis

Physical examination
Abdominal CT scan
Chest x-ray or CT scan
Abdominal MRI (if indicated)
Bone scan (if indicated)
Head CT scan or MRI (if indicated)

After taking a detailed medical history and performing a physical examination, the physician will order (or review previously performed) radiographic imaging. Most commonly, an abdominal CT scan with intravenous (IV) contrast is used to diagnose and stage kidney cancer. In cases in which contrast cannot be given because of allergy or renal dysfunction, a non-contrast CT scan or MRI can be performed. The appearance of the kidney on radiographic imaging helps differentiate benign lesions from kidney cancer, provides important staging information, and helps determine the best treatment approach.

Staging for kidney cancer
Clinical staging is performed with Physical Examination, Abdominal CT scan, and Chest X-Ray. In cases of advanced or high-risk disease, additional testing such as MRI and Bone Scan may be necessary.

The prognosis of kidney cancer is directly linked to the stage of disease. Staging is a process that demonstrates how far the cancer has spread. Both the treatment and prognosis (or outlook) for kidney cancer depend significantly on the stage of disease.

TNM SYSTEM
Status
T0	No evidence of primary kidney tumor
T1	Tumor 7 cm or less limited to the kidney
T1a	Tumor > 4 cm limited to the kidney
T1b	Tumor >= 4 cm but <=7 cm limited to the kidney
T2	Tumor more than 7 cm limited to the kidney
T3	Tumor extends into major veins or invades perinephric tissue
T3a	Tumor invades adrenal gland or perinephric tissue
T3b	Tumor extends into renal vein or infra-diaphragmatic vena cava
T3c	Tumor extends into supra-diaphragmatic vena cava
T4	Tumor invades beyond Gerota’s fascia
N0	No regional lymph node metastasis
N1	Metastasis in a single regional lymph node
N2	Metastasis in multiple regional lymph nodes
M0	No distant metastases
M1	Distant metastasis

Treatment
Most kidney cancers are localized and can be managed with surgery. Treatment for localized kidney cancer include:

Partial nephrectomy
Radical (total) nephrectomy
Ablative therapy (radiofrequency ablation or cryosurgery)
Active Surveillance (observation)

Partial nephrectomy – or removal of the tumor without removal of the entire kidney – is often recommended in cases of smaller kidney tumors, in patients with a single kidney or tumors in both kidneys, or in settings of impaired renal function. A partial nephrectomy may also be recommended in patients with Diabetes or Hypertension to preserve as much renal function as possible, even if the opposite kidney is normal. Currently, partial nephrectomy is most commonly used in tumors measuring £ 4 cm, although other factors impact whether or not a partial nephrectomy is possible or necessary. Partial nephrectomy can be performed either laparoscopically or with open surgery. In general, laparoscopic surgery is indicated for exophytic (the lesion protrudes from the kidney’s surface) tumors. Open surgery, however, may be indicated in more complex cases (larger tumors, centrally located tumors or solitary kidneys). Laparoscopic and open partial nephrectomy are as effective as total or radical nephrectomy of early stage (stage T1) kidney cancer.

Radical nephrectomy consists of removal of the entire kidney with the surrounding tissue and is most often used in cases in which a partial nephrectomy is not feasible because of tumor size or location. Radical nephrectomy is also the standard treatment for high-risk kidney cancers. For advanced stage kidney cancer, lymph node dissection, removal of other affected organs or structures, or tumor thrombectomy (removal of tumor thrombus from the vena cava) may be performed in conjunction with radical nephrectomy. Total nephrectomy may also be recommended in the setting of metastatic disease followed by systemic immunotherapy.

Ablative therapies use radiofrequency energy and extremely low temperatures to cause tissue destruction. Currently, the use of ablative therapies is limited to tumors >= 3 cm, peripherally located tumors because of limitations in the spread of the ablative effect. In addition, the effectiveness of ablative therapy compared to extirpative surgical therapy (partial and radical nephrectomy) is still under investigation. As a result, ablative therapy is most commonly used in older or medically unhealthy patients for whom the risk of surgical is too great.

Active surveillance of small, early-stage, low-risk kidney cancers may be an option for those not interested in (or candidates for) surgery or ablative therapy, and consists of periodic re-imaging to determine the rate of tumor growth. In general, active surveillance may be appropriate in older individuals with small (>= 3 cm) kidney tumors for whom the risk of surgery is too great. Detection of uncharacteristic growth may prompt a decision regarding initiation of active treatment.

Regionally advanced and metastatic kidney cancer presents several management challenges because renal cell carcinoma is not responsive to radiation therapy or traditional chemotherapy. As stated earlier, surgery may play a role, particularly in younger patients with adequate performance status. In cases of regional lymph node metastases or solitary distant metastases, such as a single lung nodule, radical nephrectomy combined with surgical removal of the metastases is often recommended as a standard treatment approach. Systemic immunotherapy using interferon and interleukin-2 augments the ability of the immune system to fight the cancer has been used in metastatic disease with some effectiveness; approximately 15% of patients have a partial response, and between 3 to 5% have a complete response with regression of their cancer. Currently, newer targeted agents known as tyrosine kinase inhibitors are being used to fight high-risk and metastatic kidney cancer. These agents act by targeting key regulatory pathways in cancer cells needs for cell survival. Tyrosine kinase inhibitors are being used in recurrent and metastatic disease, and are now being tested as an adjunct to surgery in high-risk localized disease to decrease the chances of recurrence.

Bladder cancer is the second most common urologic cancer in adults. There are 67,000 new cases of bladder cancer each year in the United States. Bladder cancer tends to occur most commonly in individuals over the age of 60 and is about 2 to 3 times more common in men than in women. Cigarette smoking and exposure to certain industrial chemicals (derivatives of compounds called arylamines and petrochemicals) are strongly associated with the development of bladder cancer.

Transitional cell carcinoma, also known as urothelial carcinoma, is the most common type of bladder cancer. Transitional cell bladder cancer may present in several different forms, including:

Carcinoma in situ (CIS)
Papillary carcinoma
Sessile carcinoma

The depth of invasion, involvement of the bladder muscle and invasion into the lymphovascular spaces determine the risk, prognosis and treatment. Bladder cancer can be classified into two broad categories – non-muscle invasive and muscle invasive urothelial carcinoma.

Non-muscle invasive bladder cancer

At the initial diagnosis, approximately 70% of patients with TCC have non-muscle invasive papillary cancers, but 50-70% of these patients have a recurrence within 5 years of treatment. Ten to twenty percent of superficial lesions progress to deep muscle invasive disease. Papillary tumors respond well to conservative treatment and are easily removed endoscopically (through a camera without a surgical incision). The rate of recurrence is approximately 70%; therefore additional treatment to prevent recurrence is usually prescribed in the form of intra-vesical therapy (placed directly into the bladder) and follow-up examinations are important. CIS tends to cause symptoms more frequently and may signal biologically aggressive disease. The risk of progression is 4-8% with some patients having a more rapid progression than papillary tumors. The overall 5-year survival for patients with non-muscle invasive and localized bladder cancer is greater than 92%.

Muscle-invasive and advanced bladder cancer
Between 20 and 25% of new cases of bladder cancer are muscle-invasive. Muscle-invasive bladder cancer is more aggressive than non-invasive disease, and approximately 50% of patients with muscle invasive disease will experience distant recurrence following therapy. Survival depends on disease stage and treatment; for organ-confined disease treated with surgery and in cases responsive to chemotherapy before cystectomy, 5-year survival is 85%. Common sites of metastasis include regional lymph nodes, bone, liver and lung. Survival decreases with more advanced disease. Five-year survival is approximately 50% in regionally advanced (lymph node positive) bladder cancer and <10% in the presence of distant metastases.

Signs & Symptoms

Hematuria
Visible
Microscopic
Irritative urination symptoms
Pain
Burning
Frequency
Incomplete emptying

For the majority of people, the first symptom of bladder cancer is blood in the urine called hematuria. Hematuria is either gross (viewable with the naked eye) or microscopic.
Irritative urination symptoms may also be associated with bladder cancer and include pain and burning on urination, frequency, and incomplete emptying of the bladder.

Diagnosis

Cystoscopy
Biopsy
Intravenous pyleogram (IVP)
Transurethral resection(TUR)
Urine testing/cytology

After taking a detailed medical history, the urologist will examine a urine specimen and check for evidence of blood and signs of infection.

The gold standard for the evaluation of the lower urinary tract is direct visual examination with a specialized instrument call a cystoscope. A cystoscope is a small camera inserted into the bladder. The purpose of routine outpatient cystoscopy is to evaluate the lining of the bladder and the urethra, the channel where urine passes out of the bladder and then exits the body. If abnormalities such as tumors or patches of abnormal-appearing tissue are discovered during cystoscopy, a biopsy or a sample of tissue may be taken at that time to determine the presence of cancer.

Because transitional cell carcinoma can also occur in the lining of the ureters and kidneys, routine surveillance of the upper tracks is also important following a diagnosis of bladder cancer. Several tests can be used to evaluate the upper tracks, including IVP and CT scan. An IVP is a conventional X-ray test using dye to examine the kidneys and ureters, tubes that transport urine from the kidneys to the bladder. This x-ray will look at the collecting system of the kidneys to determine the presence of an abnormality. A CT scan (Computed Axial Tomographic Scanning) and an MRI (Magnetic Resonance Imaging) are two tests which may be ordered in addition to the IVP to give the urologist further information needed.

Urine specimens will also be examined for abnormal cells. High grade tumors readily shed tumors cells into the voided urine allowing for pathologic examination of the urine specimen (cytology) for the presence of tumor cells.

Staging for bladder cancer
Clinical staging is performed with transurethral resection (TUR), CT scan, and exam under anesthesia (EUA). EUA allows the surgeon to manually assess the bladder after TUR for the presence of tumor.

Prognosis of bladder cancer is directly linked to the stage of the bladder cancer. Staging is a process that demonstrates how far the cancer has spread. The treatment and prognosis or outlook for bladder cancer will depend significantly on its stage.

TNM SYSTEM
Status
T0	No primary bladder tumor present
Tis	Carcinoma in situ
Ta	Noninvasive papillary carcinoma
T1	Tumor invades supepithelial connective tissue
T2	Tumor confined to the bladder muscle
T2a	Tumor invades superficial muscle (inner half)
T2b	Tumor invades deep muscle (outer half)
T3	Tumor extends through the muscle (extravesical extension)
T3a	Microscopic extravesical invasion
T3b	Macroscopic extravesical invasion
T4	Tumor invades prostate, uterus, vagina, pelvic wall, abdominal wall
T4a	Tumor invades prostate, uterus, or vagina
T4b	Tumor invades pelvic wall or abdominal wall
N0	No regional lymph node metastasis
N1	Metastasis in a single node < 2 cm
N2	Metastasis in a single or multiple node 2-5 cm
N3	Metastasis in a single or multiple node > 5cm
M0	No metastasis
M1	Distant Metastasis

Treatment
The majority of bladder cancers arise from the lining of the bladder (non-invasive tumors). Treatment for non-muscle-invasive bladder cancer can include:

Cystoscopy with cautery destruction of the tumor
TUR (Trans-Urethral Resection)
Intra-vesical drug therapy

Most modern cystoscopes are equipped with channels that permit small instruments to be passed into the bladder for the purpose of removing tissue, stopping bleeding with a special electrical device called an electro cautery or even performing laser treatment. If the bladder cancer is small enough this cautery may be used to remove the cancer.

A Trans-urethral resection is a procedure performed through the cystoscope whereby the tumor is resected without making a visible incision on the body. A small T.V. camera is inserted into the bladder to visualize the bladder. The entire removal of a bladder tumor can be accomplished through this operative cystoscope.

Drug therapy after TUR is commonly prescribed for patients with tumors that are large, multiple or high-grade. Intra-vesical therapy is the use of one of several different types of medical therapies placed directly into the bladder through a urethral catheter. Therapies consist of drugs placed in the bladder in an attempt to minimize the risk of tumor recurrence and progression. These drugs come from a wide variety of sources. About 50-68% of patients with superficial bladder cancer have a very good response to intra-vesical therapy. The most commonly used intra-vesical is Bacille Calmette-Guerin (BCG), which is administered once a week for 6 straight weeks. BCG is a weaken tuberculosis (TB) bacterium. Maintenance therapy (repeated therapy on a regular basis) with BCG or another drug administered intermittently following initial diagnosis and treatment of superficial bladder tumor decreases the likelihood of recurrence.

The biopsy specimen or TUR specimen is sent to the pathologist who will evaluate the specimen for the presence, extent, and aggressiveness of cancerous cells. Surveillance is required after diagnosis for bladder cancer. Patients are generally monitored every 3 months for the first year or two, then every 6 months for a year or two, and once a year thereafter with a cystoscopy and a urine test for cancer (called urine cytology).

Invasive bladder cancer is cancer that has invaded into the bladder wall or outside the bladder. Invasive bladder cancer treatment options are drastically different than those for superficial bladder cancer.

Treatment for invasive bladder can include:

Cystectomy with urinary diversion - In men, the bladder and prostate are identified and dissected and removed. In women, the bladder, uterus, fallopian tubes, ovaries and anterior portion of the vagina are identified and dissected and removed. Surrounding lymph nodes are removed to assess the extent or spread of the cancer. Next, one of several reconstruction options are available to replace the removed bladder

Chemotherapy - Chemotherapy is a systemic treatment (i.e., drug that is dispersed throughout the entire body) that is designed to kill cancer cells. Typically, it is administered intravenously (through a vein). The chemotherapy may be administered before surgery (neoadjuvant therapy), after surgery (adjuvant therapy) or in the setting of advanced disease. On the other hand in patients with non-invasive bladder cancer, chemotherapy may be infused into the bladder through the urethra (called intravesical chemotherapy) in hopes of reducing recurrence and progression of disease.

Radiation therapy with chemotherapy - Radiation uses high-energy x-rays to destroy cancer cells. The addition of systemic chemotherapy renders cancer cells more susceptible to the killing effects of radiation. Radiation therapy is also used to relieve symptoms (called palliative treatment) of advanced bladder.

Epidemiology & Etiology

Testicular cancer is the most common malignancy in men between the age of 15 to 35 years. Fortunately, it is one of the most curable cancers due to early diagnosis, new treatment such as cisplatin chemotherapy and a greater understanding of the nature of the disease.

There are approximately 8000 newly diagnosed cases of testicular cancer each year in the United States. The probability that an American white male will develop testicular cancer in his lifetime is approximately 0.2%. Most tumors occur in late adolescence or early adulthood. However, occasionally tumors are seen in infancy and in patients over the age of 60 years. The incidence of testicular tumors in African Americans is dramatically less than that in American whites.

Types of Testicular Cancer

Seminoma
Non-seminoma
Embryonal carciroma
Choriocarcinoma
Yolk sac tumor
Teratoma

The cancer type determines its biological behavior, thus, distinguishing the type (seminoma vs. non-seminoma) is important in making treatment recommendations. It is not unusual to have multiple cell types in a given testicular cancer (i.e. embryonal carcinoma and teratoma together).

Some testicular tumors produce proteins which can be detected in the blood and can be used as tumor markers to detect and survey disease. The most common tumor markers produced by testicular cancer are alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH). These tumor markers should normalize following successful treatment, and persistently elevated markers usually indicate presence of active disease. Most testis cancers (70%) are diagnosed at an early stage (while still confined to the testicle). However, nearly 20% of cases present with regional lymph node (retroperitoneal) involvement and approximately 10% present with distant metastasis. In general, survival rates are excellent following treatment; 5-year survival for local, regional and distant disease is 99%, 96% and 71%, respectively.

Signs & Symptoms

Most patients notice a mass, pain or swelling in one testicle. In about 10% of patients, acute pain is a presenting symptom. In a very small percentage of patients, the first symptoms are from metastases, including neck mass, problems with breathing (cough or shortness of breath), difficulty eating, abdominal pain, back pain or pain in the bones.

Diagnosis

Typically the patient or a physician feels a mass within the testicle. It is not unusual to have small lumps in the epididymis, however, any unusual mass should be evaluated by a physician. Other diseases that can cause swelling or tenderness in the testicles include infection, fluid around testicles, hernia or testicular torsion. An ultrasound examination of the scrotum and testicle is the most reliable technique to evaluate the presence of a testicular tumor.

Early detection is important, so monthly self-examination is recommended. This is best performed in a warm shower. Any suspicious areas should be examined by a physician. If an intratesticular mass is present a radical orchiectomy – removal of affected testicle and spermatocord – should be performed.

Staging for testicular cancer
Testicular tumors are staged using the TNM system. Tumors are staged based on the findings at the surgery to remove the testicle including; the microscopic examination, serum tumor markers, chest x-ray, CAT scan and other studies as indicated. Staging helps in assessing risk and in making treatment recommendations.

TNM SYSTEM
Status
T0	No evidence of primary testicular tumors
T1	Tumor confined to the testicle without lymphovascular invasion
T2	Tumor invading outside the capsule of the testicle or with lymphovascular invasion
T3	Tumor invading the spermatic cord
T4	Tumor invading the scrotum

Nx	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastases
N1	Lymph node metastases 2 cm or less in greatest dimension, less than 5 positive nodes
N2	Lymph node metastases more then 2 cm but not more than 5 cm in greatest dimension, or greater than 5 positive lymph nodes
N3	Lymph node metastases greater than 5 cm in greatest dimension

Mx	Distant metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis
M1a	Nonregional nodal or pulmonary metastasis
M1b	Distant metastasis other than to nonregional lymph node and lungs

Sx	Marker studies not available
S0	Markers within normal limits
S1	LDH < 1.5 x Normal AND hCG < 5000 mIu/mL AND AFP < 1000 ng/mL
S2	LDH 1.5-10 x N OR hCG 5,000 to 50,000 mIu/mL OR AFP 1000-10,000 ng/mL
S3	LDH > 10 x N OR hCG > 50,000 mIu/mL OR AFP > 10,000 ng/mL

Testis tumors can spread by one of three routes. First and most commonly, they may spread through the lymph nodes in the back and abdomen. Right-sided tumors tend to spread to the right side of the lymph nodes and left-sided lymph nodes in the back. Second, they may spread to adjacent tissue through the wall of the testicle into the blood supply or tubes that transport sperm. Finally, testicular tumors can initially spread by the bloodstream to distant organs such as the lung, bone or brain.

Treatment

Where testicular cancer is probable, is best to treat it initially by removing the testicle through an incision in the groin. Once the tumor is removed, any elevated tumor markers should return to the normal range. If they do not normalize, one should suspect that cancer is still present. Depending upon the examination, tumor markers, results of X-rays and type of tumor present on microscopic evaluation, a variety of different treatment options may be recommended.

In patients with low stage seminoma, removing the testicle and radiation to the back may be appropriate. With other types of tumors, initial chemotherapy or surgery to remove the lymph nodes in the back may be necessary.

Traditional surgery removes the retroperitoneal lymph nodes located in back of the abdomen. For low stage disease, the lymph nodes can be observed, treated with a short course of chemotherapy, or treated with a lymph node dissection. Most often, surgery is performed through an open incision to allow complete removal of all potentially involved lymph node tissue. In some cases, laparoscopic surgery may be used to remove the lymph nodes.

At the University of Florida, Department of Urology, conventional (open) and laparoscopic radical and partial nephrectomy is performed by several experienced fellowship-trained surgeons. Our surgical team includes Drs. Chester Algood, Benjamin Canales, Phillip Dahm, Scott M. Gilbert, Sijo Parekattil, Charles J. Rosser and Li-Ming Su.

	Chester B. Algood, MD Clinical Assistant Professor Medical Director, Urology Clinic
	Benjamin Kirk Canales, MD, MPH Assistant Professor of Urology
	Phillip Dahm, MD, MHSc Associate Professor Director of Clinical Research
	Scott M. Gilbert, MD, MS Assistant Professor of Urologic Oncology Medical Director, Urology Quality & Safety Program
	Sijo J. Parekattil, MD Co-Director of Robotic Surgery Director of Male Infertility and Microsurgery Assistant Professor of Urology Adjunct Professor of Bio-Engineering
	Li-Ming Su, MD David A. Cofrin Professor of Urology Associate Chairman of Clinical Affairs Chief, Division of Robotic & Minimally Invasive Urologic Surgery

To schedule an appointment with one of our surgeons, please contact the UF Shands Medical Plaza GU Oncology Clinic at 352-265-8282. For more information, directions to the Medical Plaza and local accommodations please visit: http://www.urology.ufl.edu/urocare_patientinfo.php