1. Private Cancer: Cancers of the Prostate, Testicles and Ovaries
Paolo Aquino
Internal Medicine/Pediatrics
November 2005

2. 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 with 5-yr survival of 64%
Currently 390 annual deaths from testicular cancer with a 5-year survival of 95%

3. 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

4. Testicular Cancer Risk factors Cryptorchidism
Family history of testicular cancer
Infertility
HIV
Isochromosome 12p

5. 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

6. 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
Symptoms of paraneoplastic limbic encephalitis: mood and behavioral changes, short-term memory problems, complex-partial seizures, and cognitive dysfunction- Electroencephalographic findings include focal or generalized slowing and/or epileptiform activity- unilateral or bilateral mesial temporal lobe abnormalities that show increased signal on T2-weighted images

7. 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

8. Testicular Cancer Diagnosis Imaging Serum tumor markers
Scrotal ultrasound
High resolution CT of abdomen and pelvis
Chest x-ray vs. CT
Serum tumor markers
Alpha fetoprotein
Beta-hCG
LDH

9. 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

10. 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

11. 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

12. Testicular Cancer Staging Metastases 0= no metastasis
1a= nonregional nodal or pulmonary metastasis
1b= distant metastasis other than nonregional lymph nodes and lungs

13. 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

14. Testicular Cancer

15. 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
AFP < 1000 ng/mL, Beta-hCG <5000mIU/mL, LDH <1.5x upper limit of normal

16. 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
No visceral metastases
AFP 1,000-10,000 ng/mL, beta-hCG 5,000-50,000mIU/mL or LDH x upper limit of normal

17. 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

18. Testicular Cancer Considerations Semen cryopreservation
Association with impaired spermatogenesis
No association with congenital abnormalities

19. 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
Implicated reasons= genetic and environmental

20. Prostate Cancer Risk factors Age Family history ? High fat diet
? High testosterone level

21. 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

22. 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

23. 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
Serum PSA can be measured after DRE

24. 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 ng/mL
Higher likelihood of finding organ-confined disease with serum PSA< 4 ng/mL

25. Prostate Cancer Diagnosis Serum PSA 4-10 ng/mL Serum PSA >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

26. 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

27. 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

28. Prostate Cancer Screening Life expectancy > 10 years
Age 40-50: annual DRE only
Over age 50: annual DRE + serum PSA

29. 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

30. 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

31. 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

32. Prostate Cancer Staging Radionuclide bone scan CT scan indications
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

33. Prostate Cancer Treatment Hormone therapy Orchiectomy
LHRH agonists: leuprolide, goserelin
Testosterone antagonists: flutamide, blcalutamide
Orchiectomy
Androgen-independent prostate cancer (AIPC)
Most with metastatic disease will become refractory to hormonal therapy
Controversy over use of monotherapy vs. use of complete androgen blockade with and LHRH agonist and antiandrogen

34. 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

35. 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

36. Ovarian Cancer Presentation Most present with advanced disease
Abdominal distension
Nausea
Anorexia
Early satiety
Dyspnea

37. 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
Leser-Trelat= sudden multiple seborrheic keratoses
Trousseau’s= migratory thrombophlebitis

38. Ovarian Cancer Presentation Pelvic exam Differential diagnosis
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

39. Ovarian Cancer Risk factors Increased risk Family history
BRCA-1 or BRCA-2 positive
Nulliparity
Frequent miscarriages
Medications that induce ovulation

40. 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

41. 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

42. 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

43. 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

44. Ovarian Cancer Diagnosis Exclusion of an extraovarian primary Gastric
Colorectal
Appendiceal
Breast
Endometrial

45. 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

46. 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

48. Review
Which of the following is NOT an identified risk factor for testicular cancer?
A) HIV
B) Smoking
C) Cryptorchidism
D) Infertility

49. Review
Answer: B- Smoking

50. 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

51. Review
Answer: E

52. 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.

53. 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.