Chapter 34



Chapter 34

Male Reproductive and Genitourinary Tumors

PROSTATE

Epidemiology:

• Carcinoma of the prostate is one of the most common malignancies in males in the United States

• 80% of prostate carcinomas occur in men older than 65 years

• 1 in 6 to 1 in 8 men

• Second leading cause of death in men

• African American men in the United States have the highest incidence of prostate cancer in the world

Prognostic Indicators:

• Strong prognostic indicators in prostate carcinoma are the clinical stage and pathologic grade of tumor differentiation

o Larger and less differentiated tumors are more aggressive and have a greater incidence of lymphatic and distant metastases.

• Age: changing hormones

• Race: African American males present with more advanced disease

• PSA: curable if caught early

• Lymph node status:

o The presence and location of lymph node metastases have significance

o Lower disease free survival rates with pelvic nodes positive for tumor

o 90% of patients with nodes positive for tumor develop distant disease.

Anatomy:

• The prostate gland surrounds the male urethra between the base of the bladder and the urogenital diaphragm.

• The prostate is a walnut shaped, solid organ that consists of fibrous, glandular and muscular elements.

Local Growth patterns:

• Most prostate carcinomas are multifocal and develop in the peripheral glands of the prostate

• Benign prostatic hyperplasia arises from the central portion

• Tumor may extend into and through the capsule of the gland, invade periprostatic tissues and seminal vesicles and if untreated involve the bladder neck or rectum

• The tumor may invade the perineural spaces, lymphatics, and blood vessels producing lymphatic or distant metastases

Distant Metastases:

• Tumor size and differentiation affect the tendency of prostatic carcinoma to metastasize to regional lymphatics.

o Periprostatic and obturator nodes followed by external iliac, hypogastric, common iliac, and periaortic nodes

o Presacral nodes (promontorial and middle hemorrhoidal group)

o Metastases to paraaortic nodes

• Patients with pelvic lymph node metastases are more likely to develop distant metastases than those with nodes negative for tumor

Clinical Presentation:

• Decreased urinary stream, frequency, difficulty in starting urination, dysuria, and infrequently even hematuria

o May also be caused by conditions other than cancer, such as benign prostatic hypertrophy (enlargement of the prostate gland, leading to narrowing of the urethra) and infection.

• Bone pain or other symptoms associated with distant metastasis are seen less frequently at the time of the initial diagnosis

• TERP: transurethral resection: a surgical procedure of the prostate performed for lower urinary tract obstructive symptoms

Detection and diagnosis:

• Complete physical and rectal examination are mandatory

o Approximately 50% of prostatic nodules found during rectal examination are confirmed to be malignant at the time of a biopsy

• A transrectal ultrasound guided needle biopsy (needle aspiration) is the standard method of diagnosis in the United States

o There are no specific characteristics on transrectal sonograms that differentiate benign prostatic disease from malignancy- therefore biopsy is required

Screening:

• Carcinoma of the prostate can be asymptomatic until reaching a significant size

• An annual digital rectal examination of the prostate should be performed in all men older than 50 years; 40 if family history

• PSA blood levels are routinely obtained

o A normal PSA is said to be 0.4 to 4.0 ng/ml

• PSA level must be adjusted for age

o A 49 yr old man: normal PSA less than 2.5 ng/ml

o 70 yr old man 6.5 ng/ml

• An elevated PSA with no palpable disease of the prostate is now the most common presentation.

Pathology and staging:

• Most malignant tumors of the prostate are adenocarcinomas

• Gleason devised a quantitative histologic grading system based on the morphologic tumor characteristics

o Primary pattern: degree of differentiation of the tumor

o Secondary pattern: glandular pattern, distribution of glands, stromal invasion; less frequent

o The primary and secondary tumor grades are labeled from 1 to 5, then added

• The Gleason score correlates closely with prognosis

o Lower scores representing more slowly growing, nonaggressive tumors

o Higher scores their more invasive metastatic counterparts

▪ 2-4: well differentiated

▪ 5-7: moderately differentiated

▪ 8-10: poorly differentiated

• Histologic differentiation of the tumor was strongly correlated with the incidence of distant metastases and survival but not as closely with locoregional failure

Stage:

• T1: lesions are not detectable on digital rectal examination

• T2: tumors are palpable and confined within the capsule of the prostates gland

• T3: lesions are more locally extensive (extracapsular invasion, seminal vesicle involvement)

• T4: tumors are fixed to the pelvic sidewall or invade adjacent structures such as rectum of bladder

Treatment techniques:

• Localized carcinomas of the prostate has a fairly slow clinical course

• Radical prostatectomy and radiation therapy are effective treatments in appropriately selected patients for tumors limited to the prostate

• Observation is reasonable management for patients older than 75 years

o It can also be offered to younger patients, with small, well differentiated tumors

• Prostatectomy: patients with resectable stage T1 or T2 prostate cancer who are in good general medical condition and have a life expectancy of at least 10 years are candidates

o 80-85% PSA progression-free at 10 years

• Impotency: dependent on patient are definition of potency and degree of potency pretreatment

o 40-60% ( nerve sparing surgery

o 100% ( radical prostatectomy

o 30-60% ( radiation

o 20-30% ( implants

• For stage T3 disease, most urologists and radiation oncologists agree that external beam radiation is the treatment of choice with hormonal therapy.

• Implants: I-125 and palladium-103 (Pd-103) are the permanent sources used with transperineal template ultrasound guided approach for low grade tumors

Hormonal therapy:

• Used to reduce metastatic tumor burden and palliate symptoms and with radiation in advanced high grade tumors

• Testosterone ablation helps by reducing tumor bulk locally and also by controlling microscopic clinically undetected metastatic disease

• Prostate tumor regression and diminished serum acid phosphatase (enzyme) levels after orchiectomy or estrogen administration

o Orchiectomy removes 95% of circulating testosterone and is followed by a prompt long lasting decline in serum testosterone levels

o Estrogen (antiandrogen) appears to suppress pituitary gonadotropin, causing reduced stimulus for testicular testosterone synthesis

• Gonadotropin releasing hormone agonists such as Zolodex and Lupron cause decline in gonadotropin and testosterone levels.

o Results similar to orchiectomy

• Flutamide is a nonsteroidal antiandrogen that inhibits androgen uptake and nuclear binding in the prostate cancer cell

Chemotherapy:

• For patients for whom hormonal therapy has failed

• Adriamycin and 5-FU used

External Radiation:

• Treating the seminal vesicles results in a larger volume of rectum irradiated

• A four field box technique with lateral portals is usually used initially if lymph nodes are to be treated

o Superior border is at the midsacral level

o Inferior border determined by the inferior most aspect of the prostate

o The lateral margins of the anterior field are 1.5 to 2 cm from the lateral pelvic brim

▪ The anterior margin is 1 cm posterior to the projection of the anterior vortex of the pubic symphysis

▪ Posterior border is generally at the posterior ischium with shielding of the posterior rectal wall as appropriate

Simulation:

• Patients are most often simulated in the supine position

• Isocenter set within the prostate

• Six field consisting of a right and left lateral pair and two parallel opposed oblique pairs 45 degrees off lateral

• Immobilization with foaming cradle or vac loc- rotation of feet will rotate hips causing tumor movement

• Barium or a plastic catheter with radiopaque markers can be used to define the rectum

• IMRT (higher energy photons used) in conjunction with BAT (most common)

• The dose to pelvic nodes is typically 50 Gy

• Prostate doses may range from 68 to 71 Gy

Interstitial Brachytherapy:

• Transrectal ultrasound with transperineal template technique with anesthesia uses a grid or template against the perineum with the patient in the dorsal lithotomy position

o Transrectal ultrasound used to direct the needles

o Seeds are distributed throughout the prostate 1 cm apart

o 25 needles and 100 or so seeds used

o I-125 (half life 60 days- 145 Gy) and palladium-103 (Pd-103) half life 17 days 125 Gy

• High dose rate iridium-192: a temporary implant technique used with EBRT

o Doses have ranged from 400 cGy in each of three functions to 900 cGy for two fractions.

o 8000 cGy to prostate

o 5000 cGy to bladder

Palliative radiation:

• Irradiation doses of 3000-4500 Gy may be effective in the treatment of massive locally extensive prostatic carcinoma or significant size pelvic lymph node disease, which may produce pain, hematuria, urethral obstruction or leg edema

• Osseous sites are treated with localized fields

• Skeletal sites treated with strontium 89 can be administered intravenously with some degree of pain relief occurring in 80% of patients.

Side effects:

Surgery:

• The most significant morbidity is incontinence and sexual impotence

Radiation therapy:

• Acute gastrointestinal side effects: diarrhea, abdominal cramping, rectal discomfort and occasionally rectal bleeding, which may be caused by transient proctitis

• Late: proctitis rectal bleeding and ulceration

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PENIS AND MALE URETHRA

Epidemiology:

Penis:

• Relative rare in the United States

• Less than 1% of cancers in men

• Higher incidence of HPV

• Circumcision performed early in life protects against carcinoma of the penis,

• Phimosis (narrowing of the opening of the prepuce)

• Smegma (a white secretion that collects under the prepuce of the foreskin) is carcinogenic in animals

Urethra:

• Rare

• Cause unknown

• Some correlation exists between the incidence of carcinoma of the urethra and chromic irritation and infections, venereal diseases, and stricture

• The average age of at the time of presentation is 58 to 60 years

Prognostic indicators:

Penis:

• The extent of the primary lesion and status of the lymph nodes

o Tumor free regional nodes imply an excellent long term disease free survival rate: 85% to 90%

o Patients with involvement of the inguinal nodes do considerably worse (40-50%)

o Pelvic node involvement implies an even worse prognosis (less than 20%)

Urethra:

• Varies considerably with the location of the primary lesion

o The prognosis for distal lesions is generally similar to that for carcinoma of the penis

o Tumors of the prostatic urethra have prognostic features similar to those of bladder carcinoma

o Superficial lesions have a good prognosis

Anatomy:

Penis:

• Two corpora cavernosa and the corpus spongiosum

• Lymphatics: inguinal nodes

Urethra:

• Divided into four sections:

o Membranous urethra: the portion passing through the urogenital diaphragm,

o Prostatic urethra: passes through the prostate

o The penile urethra: passes through the pendulous part to the penis

▪ Lymphatics: superficial and deep inguinal lymph nodes

o Bulbous urethra: dilated proximal portion of the anterior urethra

▪ External iliac, obturator and internal iliac, and presacral lymph nodes

Clinical presentation:

Penis:

• The presence of phimosis may obscure the primary lesion

• Secondary infection and an associated foul smell are common, whereas urethral obstruction is unusual

• Half of all inguinal lymph nodes are palpable at the time of presentation

• Enlargement of the lymph nodes is often related to inflammatory processes

Urethra:

• Urethral carcinoma may exhibit obstructive symptoms, tenderness, dysuria, urethral discharge, and occasionally initial hematuria (blood in the urine)

• Palpable inguinal lymph nodes at the time of presentation

Detection and diagnosis

Penis:

• Lesions seen on examination, documented by biopsy

Urethra:

• Urethroscopy and cystoscopy

• Inguinal lymph nodes should be thoroughly evaluated

• CT

Pathology and staging

Penis:

• Well differentiated squamous cell carcinomas

Urethra:

• 80% well or moderately differentiated squamous cell carcinomas

Routes of spread:

Penis:

• The inguinal lymph nodes are the most common site of metastatic spread

Urethra:

• Spread to the inguinal lymph nodes (penile)

• Tumors of the bulbomembranous and prostatic urethra metastasize first to the pelvic lymph nodes

Treatment techniques

Penis:

• Therapy is usually performed in two phases: initial management of the primary tumor and later treatment of the regional lymphatics

• Surgical resection is usually a highly effective and expedient treatment modality- it may not be acceptable to sexually active patients

Chemotherapy:

Penis:

• 5-FU

• Systemic therapy is usually reserved for metastatic and recurrent disease or those lesions so advanced as to be incurable by surgery and radiation.

Urethra:

• Noninvasive carcinoma of the proximal urethra can be treated with a transurethral resection

• Involved regional lymph nodes are treated with lymphadenectomy

Radiation therapy

Penis

• A plastic box with a central circular opening that can be fitted over the penis

o The space between the skin and box must be filled with tissue equivalent material

o The box can be treated with parallel opposed megavoltage beams

o A total dose of 6500 to 7000 cGy

o Regional lymphatics treated with EBRT

Side effects and complications

Penis:

• Irradiation produces brisk erythema, dry or moist desquamation, and swelling of the subcutaneous tissue of the shaft in almost all patients

• Telangiectasia and fibrosis are usually asymptomatic, common

• Strictures at the meatus

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URINARY BLADDER

Epidemiology

• Incidence peaks in the seventh decade

• Fourth most prevalent malignant disease

• Occurs three times more often in men than in women

Prognostic indicators:

• The tumor extent and depth of muscle invasion are important factors affecting the tumors behavior and outcome of therapy (morphology, shape)

o Papillary tumors (70% of total) are usually low grade and superficial with a favorable prognosis

o Infiltrating lesions tend to be higher grade, sessile and nodular; they invade muscle, vascular and lymphatic spaces and generally have a worse prognosis

Anatomy:

• Trigone: the triangular portion of the bladder formed by the openings of the ureters and urethra orifice

• Internal iliac lymph nodes, external iliac nodes, progress to the common iliac and paraaortic lymph nodes (extensive)

Clinical presentation:

• Present with gross painless hematuria (70-80%)

• Clotting and urinary retention may occur

• Almost all patients with carcinoma in situ experience frequency, urgency, dysuria, and hematuria

Detection and diagnosis

• Complete history, physical examination

• Rectal and pelvic exam, chest x-ray examination , urinalysis, complete blood cell count, liver function tests, cystoscopic evaluation and bimanual examination performed under anesthesia; biopsy done for diagnosis, IVP

• CT or MRI is used to evaluate bladder wall thickening and detect extravesical extension and lymph node metastases

• Bone scans are obtained for patients with T3 and T4 disease and those with bone pain.

Pathology and staging

• Most bladder cancers are epithelial in origin

• 92% are transitional cell carcinomas

Routes of spread:

• Bladder cancer spreads by direct extension into or through the wall of the bladder

• Approximately 75% to 85% of the new bladder cancers are superficial

• Perineural invasion and lymphatic or blood vessel invasion are common after the tumor has invaded muscle

o Lymphatic drainage occurs via the external iliac, internal iliac and presacral lymph nodes

o The most common sites of distant metastasis are the lung, bone and liver

Treatment techniques:

• For carcinoma in situ a radical cystectomy is usually curative (rare to diagnosis- no symptoms)

Interstitial implants

• Suitable patients are those with solitary T1 high grade to T3a lesions measuring less than 5 cm whose general medical condition permits a surgical procedure

Chemo:

• Intravesicular/IV: into the bladder, 5-FU etc.

Radiation therapy:

• Four field technique AP/PA laterals; supine

• Foley catheter- 150 to 250 ml of iodinated contrast and 100 to 150 ml of air

• Portals should include the total bladder and tumor volume, prostate and prostatic urethra, and pelvic lymph nodes

o Superior: just below the sacral promontory

o Inferior: fields extend 1 cm inferiorly to the caudal border of the obturator foramen

o Lateral: 1.5 cm laterally to the bony margin of the pelvis at its widest point

▪ Anterior: 1 cm anterior to the anterior tip of the symphysis

▪ Posterior: 2 cm posterior to the tumor mass

• Patients should be treated with an empty bladder when the entire bladder is being treated to maintain an adequate margin

o The larger pelvic field, to include the bladder and pelvic lymph nodes is generally treated to a dose of 45 to 50 Gy

• During a boost field, a full bladder will reduce the amount of bladder treated to the boost dose.

o Smaller boost is taken to 65 to 70 Gy

• 3-field spares rectum

• 5 yr overall survival rate- 50%

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TESTIS

Epidemiology:

• Relatively rare

• Most common malignancy in men between 20 and 34 (up to 40 yrs)

• Incidence is lowest in Asians, Africans, Puerto Ricans, and North American blacks

• Higher rates are reported among whites in the United States, United Kingdom, and Denmark

• Cryptochidism: (undescended testes) increases the risk of intraabdominal testicular tumors

o Patients with one testicular tumor are at increased risk for developing a contralateral malignancy (5%)

Prognostic indicators

• In seminoma and nonseminomatous tumors, the tumor stage is a significant prognostic factor

Anatomy and lymphatics

• The testes are contained in the scrotum and suspended by the spermatic cords

• Responsible for testosterone production

• The lymphatics accompany the spermatic cord up to the internal inguinal ring, drain into the retroperitoneal lymph nodes, then through the thoracic duct to lymph nodes in the mediastinum and supraclavicular fossa and occasionally to the axillary nodes

Clinical presentation

• Appears as a painless swelling or nodular mass in the scrotum

• Dull ache, heaviness, or pulling sensation in the scrotum or an aching sensation in the lower abdomen

• Approximately 10% of patients have acute and severe pain

o Related to torsion of the spermatic cord

Detection and diagnosis

• Complete history and physical examination are mandatory

• Testicular ultrasound

• Beta HCG levels (elevated in 17% of patients with seminoma) and alpha feta-protein (AFP) (elevated in more than 80% with disseminated nonseminoma)

o Can be used to document persistent or recurrent cancer and may predict the responsiveness of nonseminomas to surgery or chemotherapy

• CT

• Counseling for sperm banking

Pathology and staging

• The most common type of testicular tumor is seminoma, which has three histologic subtypes: classical, anaplastic, and spermatocytic (high cure rate)

• The nonseminomatous tumors include embryonic carcinoma, teratoma carcinoma, choriocarcinoma and yolk sac tumor

• The most common single cell type is embryonal

Routes of spread

• Pure seminoma has a much greater tendency to remain localized or involve only lymph nodes

▪ Seminoma spreads orderly, initially to the lymph nodes in the retroperitoneum then mediastinum and supraclavicular fossa

• Nonseminomatous germ cell tumors of the testes more frequently spread by the hematogenous routes to lungs and liver

Treatment techniques

• High stage: surgery and chemo

• Radical inguinal orchiectomy

• Seminoma:

o Patients with stage I seminoma is radical orchiectomy and postoperative irradiation of the paraaortic and ipsilateral pelvic nodes

o The standard dose is 2500 cGy

• Nonseminoma:

o The initial treatment for nonseminoma is radical inguinal orchiectomy, followed by chemotherapy (cisplatin)

Radiation therapy

• Hockey stick field, good testes shielded (blocks, “coffee table”, clam shell) and TLD tested for dose

• Megavoltage irradiation to the paraaortic or paraaortic and ipsilateral pelvic lymph nodes.

o Superior: at the T9-T10 interface

o Inferior: at the bottom of L5 or at the top of the obturator foramen, depending on whether pelvic nodes will be treated

o Lateral: must include the paraaortic lymph nodes and ipsilateral renal hilum

• AP/PA fields

• If the primary radiation therapy field encompasses most of one kidney, care must be taken to protect at least two thirds of the kidney from receiving doses higher than 1800 cGy

• Care should also be taken to limit the radiation dose to a significant volume of the liver to less than 3000 cGy

Routes of treatment

• Rates of disease free survival for stage I testicular seminoma are in the 95% to 97% range at 5 years

• With radiation alone, tumor free survival rates range from 30-50%

• A 5-10% incidence of second malignancy has been reported in patients treated with radiation therapy for testicular seminoma

Side effects and complications

• Patients often develop nausea and occasionally diarrhea during the treatment course

o Controlled with medication

• Severe dyspepsia (indigestion) or a peptic ulcer occurs in only 3-5% of irradiated patients

• Cumulative doses above 200 cGy will likely induce permanent sterility

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KIDNEY

Epidemiology

• 2% of all new cancers and cancer deaths annually

• The average age at the time of diagnosis is 55 to 60 years

• Male to female ratio of 2:1

• Cigarette and tobacco use, obesity, and analgesic abuse correlated with an increased risk and incidence of kidney cancer

• Leather tanners, shoe workers, and asbestos workers

• Exposure to cadmium, petroleum

Prognostic indicators

• The stage and histologic grade of the tumor

o Reported 5-year survival rates are 88% for stage I (rare to diagnose)

o 67% for stage II

o 40% for stage III

o 2% for stage IV disease

• The mean survival time for patients with metastasis (unless bone mets-can survive 5 yrs or longer) at the time of diagnosis is approximately 4 months, and only about 10% of patients survive 1 year

Anatomy and lymphatics

• Located at the level between the eleventh rib and third lumbar vertebra

• 11 to 12 cm in length

• Right kidney is usually 1 to 2 cm lower than the left

• The lymphatic drainage of the kidney occurs along the renal hilum to the paraaortic and paracaval nodes

• Can involve: renal, hilar, abdominal paraaortic, paracaval, common iliac, internal iliac or external iliac nodes.

Clinical presentation:

• Classic triad: gross hematuria, a palpable abdominal mass, and pain

• Renal pelvic: gross hematuria, pain, bladder irritation

Detection and diagnosis

• Metastatic workup includes a bone scan, chest radiograph, and CT or MRI scan of the abdomen and pelvis

• An IVP can identify the tumor, determine its location, and show the function of the contralateral kidney

• Ultrasound: differentiates solid from cystic renal lesions

Pathology and staging:

• Clear cell (renal cell) carcinoma is the predominant subtype

• Transitional cell carcinoma accounts for more than 90% of malignant tumors of the renal pelvis and ureter

Routes of spread

• A tumor may spread in the following ways

o By local infiltration through the renal capsule to involve the perinephric fat and Gerota’s fascia

o By direct extension in the venous channels to the renal vein or inferior vena cava

o By retrograde venous drainage to the testis

o By lymphatic drainage to the renal hilar, paraaortic, and paracaval nodes,

o By hematogenous route to any part of the body, including the lung, liver, central nervous system, skeleton and other organs.

▪ Approximately 50% of patients with renal cell carcinoma eventually develop metastasis

Treatment techniques

• Patients with localized renal cell carcinoma T1 and T2 is radical nephrectomy, which consist of the complete removal of the intact Gerota’s fascia and its contents, including the kidney, adrenal gland, and perinephric fat

• Renal pelvic: combination chemotherapy consisting of methotrexate, vinblastime, adriamycin and cisplatinum (MVAC).

Radiation therapy techniques

• Pre-op: large field 3000-4000 cGy

• Radiation is most commonly delivered in the postoperative setting when tumor is left behind or for recurrence following surgery

• Postoperative radiation doses range from 4500 to 5500 cGy

• The remaining kidney should not receive doses above 1800 cGy

• A field reduction may be needed at 3500 cGy to ensure that no more than 30% of the liver parenchyma is irradiated to a higher dose

• Isocentric, parallel opposed AP/PA fields or posterior oblique

• Treatment plans include

o Equal weighting of POP AP/PA fields

o Bias loading (3:1 or 2:1 posterior loading)

o Other wedge pair techniques

• A shrinking field technique to reduce exposure to dose limiting adjacent structures

• High energy photons, 10MV or higher, should be used

• Used to palliate, unresectable or inoperable (liver limits dose)

Side effects

• Acute: nausea, vomiting, diarrhea, and abdominal cramping

• Fatigue, skin reactions

|CANCER |PATHOLOGY |DOSE |

|Prostate |Adenocarcinoma |68-71 Gy (higher w/IMRT) |

|Penis |Squamous cell carcinoma |65-70 Gy |

|Bladder |Transitional cell carcinoma |45 Gy; 65 w/boost |

|Testes |Seminoma |25-30 Gy (150-180/day) |

|Kidney |Clear cell (renal cell) carcinoma |45-50 Gy |

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