GU and GYN Malignancies

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GU and GYN Malignancies

• Nancy Vander Velde MD
• September 24, 2007

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Topics

• Prostate Cancer
• Testicular Cancer
• Kidney Cancer
• Cervical Cancer
• Endometrial Cancer
• Ovarian Cancer
• Gestational Trophoblastic Tumors

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Prostate CancerEpidemiology

• Most common CA in US males
• Scandinavian is highest, Asia lowest, US African
  American 1.6gt US Whites
• If 1st degree relative with prostate CA, have 2x
  risk
• Age risk increases at age 50 in whites, 40 in
  blacks
• Unproven dietary fat, vasectomy, STDs

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Epidemiology

• 234460 Estimated new cases of prostate cancer
  in the US in 2006
• 27350 Estimated number of deaths.
• At autopsy, about 60 of men have developed
  prostate cancer.
• Rates do NOT seem to correlate with socioeconomic
  status

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Screening

• DRE leads to diagnosis in only 15-25
• PSA if gt4, 15-25 will have CA (can be mildly
  high in prostate inflammation or BPH. Low
  percent free PSA, lt25, may help diagnose in pts
  with 4-10.
• ACS recommends DRE PSA annually in males gt50,
  if high risk begin at age 40.

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Screening controversies

• ACS recommends screening if life expectancy gt 10
  years.
• NCCN recommends if life expectancy . 5 years.
• Screening has resulted in decreased mortality and
  increased rates of diagnosing at low risk disease.

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Screening and Diagnosis

• PSA velocity for normal values (from JHU)
  Change in PSA over time. 3 specimens in 18
  months, if change gt.75 ng/ml/y, do BIOPSY.
• DX transrectal US and biopsy

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Prognosis

• Stage, overall health, gleason score (sum of 2
  differentiation scores on biopsy)
• Low risk of spread beyond prostate if
  PSAlt10Gleasonlt6, high risk if PSAgt20Gleasongt8
• PSA correlates with stage and tumor volume

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Treatment Local disease

• Radical prostatectomy life expectancy should be
  gt10 years. May be laparoscopic or robotic.
• Or radiation therapy (sometimes with androgen
  deprivation).
• 5 yr survival60-70.
• Follow up PSA q 6 months, DRE q year

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Expectant management

• Check PSA and DRE every 3-6 months, rebiopsy in 1
  year.
• ACTIVELY monitor and intervene if symptoms or
  progression.
• Advantage avoid side effects or unnecessary
  care.
• DO NOT consider if life expectancy gt10 years, or
  intermediate/high risk disease.

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Treatment Metastatic disease

• Orchiectomy (surgical castration)
• Or medical castration LHRH agonists /-
  antiandrogen
• Chemotherapy for hormone refractory disease
  Taxotere prednisone is the 1st chemo to show
  survival benefit (17.4-18.9 months vs 16.5
  months), and had better pain relief and quality
  of life.

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Metastatic disease

• LHRH agonist may be given with an antiandrogen
  for gt 7 days to prevent testosterone flare.
• Bisphosphonates (zometa). Risk of renal
  insufficiency and jaw osteonecrosis.

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Side effects of treatment

• Surgery incontinence, impotence (better with
  nerve sparing)
• RT irritative symptoms to bowel/bladder
• Antiandrogens (flutamide, bicalutamide,
  nilutamide) impotence, gynecomastia, hepatitis
• LHRH agonist (lupron, gosrelin) hot flashes,
  impotence, gynecomastia

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Major complicationCord compression

• Back pain, sciatic pain, paresthesia, loss of
  sphincter control (late)
• Order MRI
• Start steroids
• Radiation

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Question

• 72M c/o back pain. PE lumbar tenderness. Labs
  alk phos 450, PSA 550. Of course you do a spine
  MRI which is neg for cord compression.
  Management would be
• A. Chemotherapy
• B. Combined androgen blockade
• C. Bilateral orchiectomy

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Testicular Cancer

• Usually age 15-35, secondary peak after 60
• Rare in African Americans
• Risk factors prior testicular CA,
  cryptorchidism, Klinefelters syn
• Symptoms Painless scrotal mass, 20 may have
  hydrocele
• Curable 5 year survival is 95!!!

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Diagnosis

• Mass that doesnt transilluminate
• Infection not getting better in 2-4 weeks
• Ultrasound
• DO radical inguinal orchiectomy
• Do NOT do scrotal biopsy (may lead to tumor
  seeding)
• CT abd/pelvis CXR or chest CT

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Pathology

• Seminoma most common, usually 4th-5th decade.
  These do not secrete AFP. (A few have high BHCG)
• Nonseminoma (embryonal CA, yolk sac CA, chorioCA,
  teratoma). Usually has high AFP and BHCG.
• 15 are mixed

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Prognosis

• Seminoma good if no nonpulm visceral mets,
  intermediate if there are. There is NO POOR RISK
  group.
• Nonseminoma good if AFP, hCG, LDH not high (90
  cure). Poor if high AFP, hCG, LDH, mediastinal
  primary, nonpulm visceral mets (20-40 cure).
  Intermediate is in between.

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5 year survivals for testicular CA

• Good risk 91
• Intermediate risk 79
• Poor risk 48

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Treatment of seminoma

• Stage I (testes) OptionsSurveillance
  (monthly), radiation, or chemo
• Stage II(retroperitoneum) radiation
• Stage III(mets), or bulky II Chemo (3-4 cycles
  of platinum based cisplat etoposidebleomycin)
• BOARD QUESTION Bleomycin is assoc with
  pulmonary fibrosis

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Treatment of nonseminoma

• Stage I surveillance (or RPLND)
• Stage II and above chemo
• 15-30 on surveillance (seminoma and nonseminoma)
  will relapse. Need to have a very compliant
  patient.

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Follow up

• CXR and tumor markers q1-2 months x 2 year, then
  q 6 month, then q year
• BOARDS 80 are associated with isochrome 12p
• Recognize extragonadal GCT young male with
  mediastinal mass,/- high AFP

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Question

• 27M with testicular mass (AFP500, BhCG1000)
  undergoes inguinal orchiectomy. Path shows
  A. Seminoma
• B. Nonseminoma

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Bladder/ureteral CA

• Men gt women, peak incidence 7th decade
• Cigarette smoking
• Analgesic abuse (phenacetin) usually preceded by
  renal papillary necrosis
• Chronic urinary tract inflammation (stones,
  chronic bladder infection)
• Arylamines in rubber, paint, dye

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Epidemiology of bladder CA

• Risky occupations chimney sweep, dry cleaning
• BOARD TIP Schistosoma haematobium in 3rd world
  countries, usually squamous cell
• ALL patients with hematuria require evaluation

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Signs and Diagnosis

• Painless hematuria
• May have urgency/frequency
• Excretory urography and cystoscopy with bx and
  cytology
• CT abd/pelvis, bone scan, CXR if more advanced
  disease
• Path 90-95 is transitional cell CA

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Treatment of bladder CA

• Superficial bladder CA transurethral resection
  /- intravesical therapy (BCG, IFN). But most
  will recur in 5 years.
• Muscle invasive bladder CA radical cystectomy
• Extensive disease, poor performance status, or
  inoperable radiation /- chemo.

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Treatment of metastatic bladder CA

• Chemotherapy usually combination, (cisplatin,
  taxanes, gemzar, etc)
• Is palliative
• Response rate 40-60
• Median survival 12 months

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Kidney Cancer

• Malesgtfemale, 4-6th decade
• Most are sporadic
• Cigarettes, obesity, HTN
• Genetic association Von Hippel Lindau
• Classic triad hematuria, flank mass, flank pain
  (present in 10)
• Diagnose with contrast CT

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Paraneoplastic syndromes

• Erythrocytosis
• Hypercalcemia
• Tumor fever
• Abnormal liver functions/necrosis (even without
  mets)
• HTN

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Work up

• If cystic lesion, likely benign
• DO NOT biopsy!
• DO nephrectomy if suspicious mass on CT
• MRI may help determine surgical resection and
  vessel involvement

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Treatment of kidney cancer Local disease

• Radical nephrectomy.
• Sometimes partial nephrectomy to avoid dialysis.

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Metastatic kidney cancer

• High dose IL 2 side effects include sepsis
  syndrome, hypotension, and ICU stay. Response
  rates low (10-20). However, about 10 may have
  durable remission.
• IFN side effects include flu symptoms,
  depression. Response rates 10-20.

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Oral kinase inhibitors in metastatic kidney cancer

• Sorafenib (nexavar) hand foot syndrome,
  cytopenias
• Sunitinib (sutent) yellow skin, left
  ventricular dysfunction, cytopenias
• In previously treated patients, both have
  resulted in stable disease or partial response in
  most patients (not many complete responses).

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NEW Temsirolimus

• FDA approved May 2007
• Rapamycin analogue given weekly IV
• Inhibits mTOR kinase
• Side effects rash, muscositis, nausea, high
  triglycerides
• Prolonged survival (10.9 vs 7.3 mths) compared to
  IFN in untreated patients. Poor prognosis
  patients seem to benefit

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Treatment of metastatic kidney cancer

• Avastin (bevacizumab) targeted to vascular
  endothelial growth factor
• 2nd line therapies with the above
• Experimental therapies vaccines, BMT
• Sometimes nephrectomy is used for paraneoplastic
  syndromes or palliation. Solitary met may be
  resected.

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Prognosis

• 5 year survival stage I 75
• Stage IV 10
• Exceptions some patients may have indolent
  course, spontaneous regression, or disease free
  after metastatectomy

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Cervical Cancer Epidemiology

• Less common in US, but 2nd cause of cancer death
  in developing countries
• Low socioeconomic class/lack of health care
• Related to number of sexual partners, age at
  intercourse (lt16yrs)
• 90-100 associated with HPV (types 16,18,33,35)

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Epidemiology

• Cigarettes
• HIV
• Controversial OCPs
• Symptoms intermenstrual or post-coital bleeding

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Screening the Pap smear

• ACOG recs pap yearly for gt18 or sexually active
• Do not need pap if routine hysterectomy
• Pap smear has reduced risk of death by 90!
• Controversial to do pap in those gt70yrs

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Pap screening

• NCCN recommends pap q 2-3 years if gt30 years and
  3 negative consecutive cytologies.
• If HPV DNA testing negative, and gt 30 years, and
  pap negative, can do HPV DNA pap q 3 years.
• Exceptions HIV, DES exposure, and h/o cervical
  CA still require yearly pap.

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Diagnosis and work up

• If pap is abnormal, but exam is normal, do
  colposcopy (CA will look white, or atypical blood
  vessels).
• If suspicious lesion, but normal pap, do biopsy.
• If obvious cancer, skip the pap and do biopsy.

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Abnormal pelvic exam
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Treatment of cervical CA

• Pathology Squamous cell is most common.
• Microscopic CA only simple hysterectomy
  (standard) or cone biopsy if wants fertility.
• Local disease radical hysterectomy

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Treatment of cervical CA

• If bulky disease (gt5cm), node positive, or
  positive margins cisplatin based chemo RT
  (pelvic vaginal brachtherapy)
• Locally recurrent disease Pelvic exenteration
  or radiation /- chemo
• Chemo for mets (usually mets to bone or lung)

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Surveillance after treatment for early stage

• Pap smear
• q3 month x 1 year, then
• q 4 month x 1 year, then
• q 6 month x 3 year, then
• q year after that

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HPV vaccine

• Quadravalent HPV 6/11/16/18 L1 VLP (Gardisil) is
  available.
• ACP recommend for females age 9-26
• Given at 0,2, 6 months.
• Is NOT effective if abnormal cytology or HPV
  infection.
• No serious events in 4 years of follow up so far.

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HPV vaccine

• Protects against CIN due to HPV 6, 11, 16, and 18
  occurred in 100 of subjects in a placebo
  controlled trial.
• Also had decrease in genital warts.
• Note cervical screening is STILL NEEDED because
  other HPV types may cause disease!!

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Unanswered questions with the HPV vaccine

• Duration of protection is unknown (antibodies
  persist for 4 years).
• ? Level of antibody needed for protection.
• ? Ideal age to vaccinate.
• ? Vaccine efficacy in males.

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Vaginal CA

• Associated with HPV
• Usually squamous cell
• BOARDS DES (off the market in 1970) assoc with
  clear cell adenoCA

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Endometrial CA

• 4th most common CA in women, most present stage I
• Risk factors postmenopausal, western nations
  (?high fat diet), unopposed estrogens, obesity,
  nulliparity, infertility, diabetes, HTN,
  tamoxifen, HNPCC
• Signs postmenopausal bleeding
• Diagnose endometrial biopsy or DC

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Treatment

• TAH/BSO with sampling of nodes
• Post op vaginal irradiation if low grade,
  pelvic/-vag irradiation if high grade or deep
  myometrium invasion
• Radiation alone if not surgical candidate
• Chemotherapy or progestins (if PR ) in metastatic

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Ovarian CAEpidemiology

• Age 50-75
• WhitesgtAfrican Americans
• BRCA 1 2
• HNPCC
• Nulliparity
• Oral contraceptives DECREASES the risk by about
  1/2
• Other conflicting factors (diet,talc, HRT)

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Epidemiology

• Pregnancy (esp lt25 yrs) decreases risk
• Most lethal of the gynecological cancers
• Death from intestinal obstruction and inanition
• Less common Germ cell tumors in younger women.
  Similar to testicular CA.

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Screening for ovarian CA

• There isnt any
• In high risk patients, consider oopherectomy at
  age 35, annual CA 125, vaginal US, PE. This is
  being evaluated in NIH trial.
• Most patients present in advanced stage, tumors
  can grow up to 10-12 cm before symptoms (vague,
  bloating, etc)

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Treatment simplified

• Early stage (ovary only) surgery
• Early stage but high grade surgery adjuvant
  chemo (carbo/taxol)
• Advanced stage Debulking surgery Chemo.
  Optimal cytoreduction (residual dz lt1cm) has
  better survival
• Follow with CA 125 rise indicates recurrence

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Ovarian cancer on ultrasound
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Gestational Trophoblastic Tumors

• lt1 of Gyn malignancies
• High cure rate gt95 for low risk met
• Usually after hydatidiform mole, may also occur
  after pregnancy or abortion
• Clues to a molar pregnancy no fetal heart tones,
  large uterus, early toxemia, hyperemesis
  gravidarum, hyperthyroid

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GTT

• Vaginal bleeding with positive pregnancy test
• Snow storm appearance on uterine US
• Hysterectomy if local disease and fertility not
  desired, although normal pregnancy can occur.

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Molar pregnancy
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GTT

• Mets occur 6-19, to lung, pelvis, liver, brain.
  May result in respiratory failure. Check CXR.
• Marker B-HCG. Inversely prognostic.
• Follow B-HCG weekly after molar evacuation by
  suction/curettage
• Avoid pregnancy for 1 year
• Chemo for mets

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THE END