Transcript Private Cancer: Cancers of the prostate, testicles and ovaries

Private Cancer:
Cancers of the Prostate, Testicles and Ovaries
Paolo Aquino
Internal Medicine/Pediatrics
November 2005
Testicular Cancer
• Epidemiology
– Most common solid malignancy for males 1435
– Accounts for 1% of all cancers in men
– One of the most curable solid neoplasms
• Prior to late 1970s, accounted for 11% of cancer
deaths for men 25-34 with 5-yr survival of 64%
• Currently 390 annual deaths from testicular cancer
with a 5-year survival of 95%
Testicular Cancer
• Epidemiology
– Cell types
• May consist of single predominant histologic pattern
or mix of multiple histologic types
• Two broad categories:
– Pure seminoma
– Non-seminomatous germ cell tumors (NSGCTs)
– Ratio 1:1
Testicular Cancer
• Risk factors
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Cryptorchidism
Family history of testicular cancer
Infertility
HIV
Isochromosome 12p
Testicular Cancer
• Presentation
– Nodule or painless swelling of one testicle
– Dull ache or heavy sensation in lower abdomen,
perianal region or scrotum
– 10% will present as acute pain
– Increased hCG production
• Gynecomastia
• Hyperthyroidism
Testicular Cancer
• Presentation
– 10% will present with metastatic symptoms
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Neck mass
Cough/dyspnea
Anorexia, nausea, vomiting, GI bleed
Bone pain
Nervous system
Lower extremity swelling
– Paraneoplastic limbic encephalitis
Testicular Cancer
• Diagnosis
– Bimanual examination of scrotal contents
– Any solid, firm mass within the testis is
testicular cancer until proven otherwise
– Differential: torsion, epidydimitis, hydrocele,
epididymo-orchitis, varicocele, hernia,
hematoma, spermatocele, syphilitic gumma
Testicular Cancer
• Diagnosis
– Imaging
• Scrotal ultrasound
• High resolution CT of abdomen and pelvis
• Chest x-ray vs. CT
– Serum tumor markers
• Alpha fetoprotein
• Beta-hCG
• LDH
Testicular Cancer
• Diagnosis
– Radical inguinal orchiectomy
• Histologic evaluation
• Local tumor control
– Retroperitoneal lymph node dissection
• Only reliable method to identify nodal
micrometastases
• Gold standard for accurate pathologic staging of the
retroperitoneum
Testicular Cancer
• Staging
– Tumor
• 0= no tumor
• is= carcinoma in-situ
• 1= limited to tunica albuginea without vascular or
lymphatic invasion
• 2= limited to tunica vaginalis with vascular or
lymphatic invasion
• 3= invades the spermatic cord
• 4= invades the scrotum
Testicular Cancer
• Staging
– Lymph nodes
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0= no regional lymph node metastases
1= lymph nodes less than 2 cm
2= lymph nodes 2-5 cm
3= lymph node > 5 cm
Testicular Cancer
• Staging
– Metastases
• 0= no metastasis
• 1a= nonregional nodal or pulmonary metastasis
• 1b= distant metastasis other than nonregional lymph
nodes and lungs
Testicular Cancer
• Staging
– Tumor markers
Stage
LDH
hCG
AFP
S1
<1.5x
<5,000
<1,000
S2
1.5-10x
S3
>10x
5,0001,00050,000
10,000
>50,000 >10,000
Testicular Cancer
Testicular Cancer
• Prognosis
– Good prognosis (60%): 5-year survival= 91%
• Seminoma: Stage I- IIIA/B
– No visceral metastases
– Normal AFP
• NSGCT: Stage I-IIIA
– Testicular or retroperitoneal primary tumors
– No visceral metastases
– AFP < 1000 ng/mL, Beta-hCG <5000mIU/mL, LDH
<1.5x upper limit of normal
Testicular Cancer
• Prognosis
– Intermediate prognosis (26%): 5-year survival= 79%
• Seminoma: Stage IIIC
– Testicular or retroperitoneal primary
– Visceral metastases
– Normal serum AFP
• NSGCT: Stage IIIB
– Testicular or retroperitoneal primary
– No visceral metastases
– AFP 1,000-10,000 ng/mL, beta-hCG 5,00050,000mIU/mL or LDH 1.5-10x upper limit of normal
Testicular Cancer
• Prognosis
– Poor prognosis (14%): 5-year survival=48%
• NSGCT: Stage IIIC
– Mediastinal primary
– Visceral metastases
– AFP > 10,000 ng/mL, beta-hCG > 50,000mIU/mL, or
LDH > 10x upper limit of normal
Testicular Cancer
• Considerations
– Semen cryopreservation
– Association with impaired spermatogenesis
– No association with congenital abnormalities
Prostate Cancer
• Epidemiology
– 2nd most common cancer in American men
(non-melanoma skin cancer= #1)
– Estimated 230,000 cases in 2005 with 30,000
deaths
– Increased detection rates
– 1.5% annual increase in incidence since 1995
Prostate Cancer
• Risk factors
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Age
Family history
? High fat diet
? High testosterone level
Prostate Cancer
• Presentation
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Usually asymptomatic
Elevated serum PSA
Asymmetric areas of induration
Frank nodules
Urinary urgency, frequency, hesitancy, nocturia
Erectile dysfunction
Hematuria
Hematospermia
Metastatic disease: bone pain, spinal cord compression
Prostate Cancer
• Diagnosis
– Digital rectal examination
• Evaluates posterior and lateral prostate gland
• PPV 5-30%
– PPV increases with respect to PSA concentration
• Any induration, asymmetry or nodularity require
further diagnostic studies
Prostate Cancer
• Diagnosis
– Serum PSA
• Causes of elevation
– Benign prostatic hypertrophy
– Prostate cancer
– Prostatitis
– Trauma
• Malignant prostate tissue generates more PSA than normal or
hyperplastic tissue
• Disruption of prostate-blood barrier increases serum
concentration of PSA
Prostate Cancer
• Diagnosis
– Serum PSA <4 ng/mL
• 43% of those 50 years and older with prostate
cancer had serum PSA<4 ng/mL
• 21% of cancers diagnosed without PSA had a serum
PSA of 2.6-3.9 ng/mL
• Higher likelihood of finding organ-confined disease
with serum PSA< 4 ng/mL
Prostate Cancer
• Diagnosis
– Serum PSA 4-10 ng/mL
• Biopsy advised regardless of DRE findings
• One in five biopsies done with serum PSA 4-10 ng/mL will be
positive
– Serum PSA >10 ng/mL
• Biopsy uniformly recommended
• Chance of finding prostate cancer over 50%
• Many cancers at this stage will no longer be organ-confined
Prostate Cancer
• Diagnosis
– Recommendations for prostate biopsy
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Suspected by DRE
Serum PSA as low as 2.6 ng/mL
PSA velocity > 0.75 ng/mL per year
Confirmation of elevated PSA advised prior to
proceeding with prostate biopsy
Prostate Cancer
• Diagnosis
– Biopsy
• Gold standard
• Any suspicious area + 6 tissue cores from base, midzone, and
apical areas bilaterally
• Higher cancer detection rates with more biopsies
• Complications
– Hematospermia, hematuria
– Fever
– Rectal bleeding
• No clinical data support spread of cancer due to biopsy
Prostate Cancer
• Screening
– Life expectancy > 10 years
– Age 40-50: annual DRE only
– Over age 50: annual DRE + serum PSA
Prostate Cancer
• Staging
– Determining correct stage is critical
– Major complications associated with therapies
• Risks justified if treatment has reasonable chance of
achieving a cure
– Primary goals
• Rule out disease outside of prostate gland
• Assess likelihood of finding potentially resectable,
organ-confined disease
Prostate Cancer
• Staging
– Clinical staging- frequently underestimates
extent of tumor found at surgery
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T1= not palpable, not visible on TRUS
T2= palpable, confined to gland
T3= protrudes beyond the prostate capsule
T4= fixed, extended well beyond the prostate
Prostate Cancer
• Staging
– Gleason grade
• Analysis of tumor histology
• Graded 1-5 based upon differentiation and
architecture
• Combined Gleason score of primary and secondary
score
– 2-4= low-grade
– 5-7= moderately differentiated
– 8-10= poorly differentiated
Prostate Cancer
• Staging
– Radionuclide bone scan
• Not indicated for
– Clincal T2 cancer or less
– Gleason score less than or equal to 6
– Serum PSA less than 10 ng/mL
– CT scan indications
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Gleason score greater than 6
Serum PSA > 10 ng/mL
Clinical stage T2 or greater
Design of treatment portals for external beam radiation therapy
Prostate Cancer
• Treatment
– Hormone therapy
• LHRH agonists: leuprolide, goserelin
• Testosterone antagonists: flutamide, blcalutamide
– Orchiectomy
– Androgen-independent prostate cancer (AIPC)
• Most with metastatic disease will become refractory
to hormonal therapy
Ovarian Cancer
• Epidemiology
– 2nd most common gynecologic malignancy
– Most common cause of death for gynecologic
cancer
– 4th most common cause of cancer related death
for females in the United States
– 90% are epithelial cell tumors
Ovarian Cancer
• Presentation
– Most diagnosed between 40 & 65
– Early disease has vague symptoms
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Lower abdominal discomfort, pressure
Gas, bloating, constipation
Irregular menstrual cycles
Low back pain
Fatigue, nausea, indigestion
Urinary frequency
dyspareunia
Ovarian Cancer
• Presentation
– Most present with advanced disease
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Abdominal distension
Nausea
Anorexia
Early satiety
Dyspnea
Ovarian Cancer
• Presentation
– Symptoms more typical for ovarian cancer
• Develop over shorter period of time
• Multiple symptoms
• Greater frequency and severity
– Paraneoplastic phenomena
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Humoral hypercalcemia of malignancy
Subacute cerebellar degeneration
Leser-Trelat sign
Trousseau’s syndrome
Ovarian Cancer
• Presentation
– Pelvic exam
• Solid, irregular, fixed pelvic mass
• Upper abdominal mass
• Ascites
– Differential diagnosis
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Benign neoplasms- endometriomas, fibroids
Functional ovarian cysts
TOA
Non- gynecologic masses
Metastases
Ectopic pregnancy
Ovarian Cancer
• Risk factors
– Increased risk
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Family history
BRCA-1 or BRCA-2 positive
Nulliparity
Frequent miscarriages
Medications that induce ovulation
Ovarian Cancer
• Risk factors
– Decreased risk
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Oral contraceptive use
Breast feeding
Early age of first pregnancy
Tubal ligation
Early menarche
10% decrease in risk with each pregnancy
Ovarian Cancer
• Diagnosis
– Pelvic examination
– Ultrasound
• Characteristics against malignancy
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Cystic
Unilateral
Less than 8 cm
Smooth internal and external contours
• Threshold for surgical intervention is lower for
postmenopausal women
Ovarian Cancer
• Diagnosis
– Tumor markers
• CA 125
– > 65U/mL in 80 percent of women with ovarian cancer
– Not specific
» Endometrial cancer
» Pancreatic cancer
» Endometriosis
» Fibroids
» PID
» Menstrual variation
Ovarian Cancer
• Diagnosis
– Tumor markers
• CA 125
– More useful in postmenopausal women
» PPV 97%
– Baseline measurement useful for following treatment
• Alpha fetoprotein for endodermal sinus tumor
• LDH for dysgerminoma
• Beta-hCG for nongestational choriocarcinoma
Ovarian Cancer
• Diagnosis
– Exclusion of an extraovarian primary
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Gastric
Colorectal
Appendiceal
Breast
Endometrial
Ovarian Cancer
• Diagnosis
– Histopathology
• Papillary serous ~75%
– Simulates lining of fallopian tube
• Mucinous ~10%
– Resembles endocervical epithelium
• Endometroid ~10%
– Resembles endometrial cancer
• Rare- clear cell, transitional cell
Ovarian Cancer
• Staging
– Surgery is necessary
– Occult metastases not uncommon
• More advanced disease noted in 29% of patients
thought to have stage I disease, 43% of patients
thought to have stage II
Review
• Which of the following is NOT an
identified risk factor for testicular cancer?
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D)
HIV
Smoking
Cryptorchidism
Infertility
Review
• Answer: B- Smoking
Review
• Which of the following statements about ovarian
cancer is false?
– A) Among gynecologic cancers it is the most common
cause of death
– B) Typically presents as advanced disease
– C) Tubal ligation is associated with decreased risk for
ovarian cancer
– D) Surgery is necessary for accurate staging
– E) Elevated serum CA-125 is specific for ovarian
cancer
Review
• Answer: E
Review
• A 72-year-old man with a history of localized prostate
cancer presents to his physician with pain in his ribs. He
underwent a radical prostatectomy 4 years earlier but was
lost to follow-up. A bone scan demonstrates diffuse
skeletal metastases; his serum PSA level is 97 ng/mL. The
best next step in management is:
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A) Treat with strontium-89 to relieve the patient’s pain
B) Perform a rib biopsy to rule out other malignancies
C) Perform an orchiectomy
D) Treat with flutamide alone
E) Perform a needle biopsy of the prostatectomy site to confirm
recurrent disease.
Review
• Answer: C- Perform an orchiectomy
– This patient presents with unequivocal metastatic
disease: pain, widespread osteoblastic metastases and a
highly elevated PSA. Further biopsies are unnecessary.
Treatment with strontium-89, although effective, is
toxic and should be considered only after hormone
therapy has failed. Monotherapy with flutamide is
associated with poor survival compared with the
combination of flutamide and leuprolide.