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 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

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 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

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 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 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 Implicated reasons= genetic and environmental

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 Serum PSA can be measured after DRE

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 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

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 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

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

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

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

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.