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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 – – – – – 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 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 – – – – 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) B) C) 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: – – – – – 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.