경희대학교 의과대학·의학전문대학원

비뇨생식기종양

방광암

신장암

전립선암

고환암

난소암

자궁경부암

방광암

• 발생율: 2,905명/년(2.0%, 12위), 남/녀:2,331/574

(

)

• Epidemiology: smoking

• Treatment

– Invasive: cystectomy± systemic chemotx – metastatic:etastat c:

• Curative or palliative • Adjuvant, neoadjuvant

신장암

• 발생율: 2,299명/년 (1.6%), 남/녀: 1,569 /730명 • 항암화학요법에 반응을 잘 안한다

• 생물학적치료(면역치료 등)에 반응을 한다

– Interferon alpha, interleukin-2

• 자연적으로 치유되기도 한다

신장암의 병기와 예후

병기 내용 5년 생존율

병기 내용 5년 생존율

1기 Confined to kidney 66%

2기 Invade renal capsule, confined to

Gerota fascia

64%

3기 Involve renal vein/vena cava, hilar

lymph node

42% lymph node

4기 Invade adjacent organs or distant

metastasis

신장암의 치료

• Localized tumor: stage I, II and selected III

– radical nephrectomy

• Advanced disease

C i

– Cytotoxic chemotherapy: rare response – Immunotherapy

• Interferon alpha & IL-2: 10-20% response

– Surgery

• Control pain, bleeding

• Metastatectomy: solitary or CNS

– Observation only

• Stable disease: 10% > 12 months • Stable disease: 10%, > 12 months • Spontaneous regression

– Experimental treatment

• Allogenic stem cell transplantation

– New agents

• Tyrosine kinase inhibitors, VEGF inhibitor(multi-targeted)

– Sunitinib, Sorafenib(40% response rate)

Regression of metastatic Renal-Cell Carcinoma after

Nonmyeloablative

allogenic

peripheral-

stem

-cell

transplantation

CR(3)+PR(7): 10/19(53%)

Molecular Pathways & Targeted Therapies in RCC

VEGF

VEGF

Bevacizumab

Therapeutic Targets in Renal Cell Carcinoma

Sorafenib Axitinib Sorafenib Sunitinib _Akt/PKB PI3K Raf MEK VEGFR-2 P P P P Vascular Vascular endothelial cell

plasma membrane

Rini B, et al. J Clin Oncl. 2005;23:1028-1043.

p38MAPK Erk P P permeability Endothelial cell survival Endothelial cell migration Endothelial cell proliferation

Sunitinib vs Interferon alfa in metastatic renal cell carcinoma

Sorafenib in advanced clear cell renal cell carcinoma N Engl J Med 2007;356:125-134 CR PR SD Sorafenib,N=451 1(<1%) 43(10%) 333(74%) Placebo, N=452 0 8(2%) 239(53%) HR:0.44, 95% CI 0.35-0.55; P<0.01

전립선암

• 발생율: 3,487명/년(2.4%)

• Clinical states

– 1st_{state: no cancer diagnosis: benign hyperplasia, family history}

– 2nd_{state: confined to the gland}

– 3rd_{state: rising PSA level after surgery or radiation}

– 4th_{state: detectable metastasis who have not undergone castration}

5th_{state: detectable metastasis who have had castration}

원발 부위별 발생등록분율(성별)

(2005년도)

Treatment:

Clincally localized disease

• Treatment modalities

– Radical surgery – Radiation therapy – Active surveillance

• Monitoring illness at fixed interval with no treatment • 10 year survival rate

– Radical prostatectomy 93%, RT 74%, surveillance 84%

• Case selection is critical

– Elderly men, well-differentiated tumors

• Consideration factor for choice of therapy

– Presence of symptoms

– Probability of adverse affectto untreated patient during lifetime

C bili b i l d li h b h l l & i

– Curabilityby single-modality threapy or both local & systemic therapy

• Primary outcomes

– Cancer control& treatment related morbidities

• Continence, sexual potency, bowel function

• Prognostic model

Treatment:

Rising PSA

• Definition:

– Rising PSA after surgery and/or radiation

No evidence of disease on scan

– No evidence of disease on scan

• Central issue

– Persistent disease in primary site or systemic disease

• Localized disease

– Radiation, Salvage prostatectomy

• Systemic disease

• Systemic disease

– Immediate therapy is not always required

• Median time to metastatic progression: 8 yrs • Free of metastases at 5 yrs: 63%

– Prognositc factors:

• Gleason grade of primary tumo, time to recurrence, PSA doubling times

Treatment:

Metastatic disease

• Noncastrate

• Testosterone lowering agents

– GnRH analogue: » leuprolide, goserelin

– Estrogen(diethylstilbestrol), progestational agents

• Antiandrogen

Fl t id bi l t id il t id – Flutamide, bicalutamide, nilutamide

• Castrate

– Discontinue all hormonal therapy: withdrawal response

– 2nd_-3rd_{line hormone therapy}

고환암

• Origin: primordial germ cells

• Origin: primordial germ cells

• Extragonadal

– Mediastinum, retroperitoneum, pineal gland

• Disease of young age

– 호발연령: 20-40세

백인 흑인

• 백인>흑인

• 호발지역: Scandinavia, New Zealand

• 발생율: 148명/년(한국남성암의 0.2%)

Etiology & Genetics

• Cryptorchidism

• Testicular feminization syndrome

y

• Klinefelter’s syndrome

– Mediastinal tumor

• Incidence of another testis: 2%

• Chromosome 12

– Excess copy number, i(12p)

• Tumor marker

– AFP: nonseminoma

– hCG: seminoma, nonseminoma – LDH

Treatment (1)

• Stage I, nonseminoma

– Orchiectomy

– Nerve sparing RPLND

• vascular/lymphatic invasion or extends into tunica,

spermatic cord, scrotum(T2-4) – Surveillance

• No vascular/lymphatic invasion(T1)

– Cure rate: > 95%

St

II

i

• Stage II, nonseminoma

– Modified bilateral RPLND

– High-volume(> 6 nodes, > 2cm node)

• 2 cycles of adjuvant chemotherapy

– Cure rate: > 98%

Treatment (2)

• Stage I & II seminoma

– Inguinal orchiectomy & retroperitoneal radiation

C 98%

– Cure rate: 98%

• Advanced GCT

– Stage IIc & stage III

– Chemotherapy: cisplatin containing – Cure rate: 70-80%

• Salvage chemotherapy

– 2nd_{line chemotherapy}

• Cure rate: 25%

– High dose chemotherapy & stem cell support

• Post-treatment complication

Ovarian Cancer

Incidence, Epidemiology, Etiology

• Pathologic classification

– Epithelial, stromal, germ cell tumor • 발생율: 1,544명/년(여성암 2.4%, 10위)

• Peak age: eighth decade

• Risk factors

– Infertility, nulliparity, frequent miscarriages, use of ovulation-inducing drugs(clomiphene)

– Reducing factor: pregnancy, breast feeding, oral contraceptive

• Familial syndrome

– Hereditary breast/ovarian cancer

• BRCA1&2 mutation

– Lynch type II cancer family syndrome

원발 부위별 발생등록분율(성별)

(2005년도)

Diagnosis, Screening, Pathology

• Routine pelvic examination

• CA125

– Postmenopausal women, asymptomatic pelvic mass,

CA125 ≥ 65U/ml

• Screening

– Annual pelvic examination, transvaginal ultrasound, CA125 in family history of ovarian cancer

CA125 in family history of ovarian cancer

• Subtype of common epithelial tumors

– Serous(50%), mucinous(25%), endometroid(15%), clear cell(5%), Brenner tumors(1%)

Staging, Prognostic factors

• Staging laparotomy

– Manual inspection of diaphragm, peritoneal surfaces, total abdominal hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy

• 5-year survival

– Stage I(90%), II(70%), III(15-20%), IV(1-5%)

P

i f

• Prognostic factors

– Residual disease, histologic grade, decline of CA125 – Expression of p53, EGFR

Treatment (1)

• Stage I&II, microscopic or no residual disease

– Stage I, no residuals, well/moderately differentiated:

• no adjuvant therapyno adjuvant therapy

– Stage I with poor histologic grade, stage II:

• adjuvant therapy (cisplatin based chemotherapy or

total-abdominal irradiation)

• Stage III, minimal residual tumor (<1cm)

– Combination chemotherapy (cisplatin, paclitaxel) – CR: 40-50%CR: 40 50%

• Advanced disease(Stage III, IV), bulky residual

tumor

– Combination chemotherapy followed by cytoreductive surgery

Treatment (2)

• Second-look laparotomy

• Maintenance therapy

• Recurred disease

– Disease-free interval: > 6 months

• Reinduction with same regimen

• Intraperitoneal chemotherapy

– Small residual volume (<1 cm3₎

• New drugs

– topotecan, gemcitabine, liposomal doxorubicin, – bevacizumab

자궁경부암

• 발생율: 3,737명/년 (여성암 5.7%, 6위)

Treatment

– Cone biopsy, abdominal hysterectomy

• Stage IAStage IA

– Total or vaginal hysterectomy

• Stage IB-IIA

– Radical hysterectomy, Radiation therapy

• Stage IIB – IVA

– Radical radiation

– Concurrent chemoradiotherapy

• Platinum based chemotherapy • 30-50% risk reduction

• Unresectable advanced/Recurrent

– Palliative chemothx: cisplatin, 5-FU, irinotecan – Response of combination chemotherapy: 50-60%