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

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

• Risk factors– Age– Family history– ? High fat diet– ? High testosterone level

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

• 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:– 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.