Private Cancer: Cancers of the Prostate, Testicles and Ovaries Paolo Aquino Internal...
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Transcript of Private Cancer: Cancers of the Prostate, Testicles and Ovaries Paolo Aquino Internal...
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 14-
35– 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– 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
• 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
• 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 5,000-50,000
1,000-10,000
S3 >10x >50,000 >10,000
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
5,000-50,000mIU/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
• Presentation– 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
• 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• 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• 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• 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
• 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• 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• Benign neoplasms- endometriomas, fibroids• Functional ovarian cysts• TOA• Non- gynecologic masses• Metastases• Ectopic pregnancy
Ovarian Cancer
• Risk factors– Increased risk
• Family history
• BRCA-1 or BRCA-2 positive
• Nulliparity
• Frequent miscarriages
• Medications that induce ovulation
Ovarian Cancer
• Risk factors– Decreased risk
• 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– 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
• 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?– A) HIV– B) Smoking– C) Cryptorchidism– D) Infertility
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
• 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:– 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.