11/20- Malignant Diseases of the GU system Flashcards Preview

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Flashcards in 11/20- Malignant Diseases of the GU system Deck (82):
1

What is the most common urologic malignancies? Next?

1. Prostate

2. Bladder

3. Kidney

4. Testis

2

Among men, ___ cancer is the most common.

This cancer is the #__ cause of cancer deaths in men

Among men, prostate cancer is the most common.

This cancer is the #2 cause of cancer deaths in men (2nd to lung)

3

Bladder is the #__ most common and the #__ cause of cancer deaths (among men)

Bladder is the #4 most common and the #8 cause of cancer deaths (among men)

4

T/F: There is no GU cancer in the top 10 causes of cancer in women. What is the highest?

- True; no GU cancer in top 10 women cancer cases

- Kidney cancer is #8 (only 3% of new cases)

5

What are the risk factors for Prostate cancer?

- Which is most important

- What are modifiable risk factors

- Advanced age

- African American race (more common and earlier age/higher stage)

- Family history (strongest!)

- Modifiable risk factors

  • Obesity
  • Fat intake (mono-unsaturated fats)

6

Describe family history role in prostate cancer/risks

- 2-3x increased risk of prostate cancer

- BRCA link: female relatives with breast/ovarian cancer

7

What is involved in prostate cancer screening?

- PSA: prostate-specific antigen

- DRE: digital rectal exam

  • Palpation of posterior zone of prostate
  •  Should be done annually for men > 50 yo BOTH are required

8

What is PSA? - What is it's function? - Circulation

Serine protease that is unique to prostate

- Lyses seminal coagulum

- Circulates free or bound to a-1 antichymotrypsin

- %free correlates with benign vs. malignant

  • >25%: more likely BPH
  • < 10%: at least 50% chance of being cancer
  • Only valid at total PSA values 4-10

9

Describe the expected values/diagnostic criteria levels of PSA

% free correlates with benign vs. malignant

- >25%: more likely BPH

- <10%: at least 50% chance of being cancer

- Only valid at total PSA values 4-10

10

__% of prostate cancer occurs in the ____ zone

75% of prostate cancer occurs in the posterior zone

- Habitus may make difficult; technical points

- PSA testing has caused "stage migration" (finding earlier)

11

What has US Preventive Services Task Force (USPSTF) recommends what for prostate screening?

What does American Urological Association say?

- Recommends against prostate specific antigen (PSA)-based screening for prostate cancer

- American Urological Association disagrees: all men 55-69 yo should discuss PSA screening with provider and get screened every 2 yrs

  • Little benefit to men 70+ with life expectancy under 10-15 yrs
  • Screening with PSA has reduced prostate cancer mortality
  • Screening with PSA has led to diagnosis and treatment of many indolent cancers

12

What is the sensitivity and specificity of PSA screening?

How to improve?

Overall

- Sensitivity: 35%

- Specificity: 63%

If stratify for PSA > 4:

- Sensitivity: 86%

- Specificity: 33%

13

How should we manage screening of prostate cancer?

Need to focus on age-specific! recommendations and practices (and tx need to maximize cure and minimize ASEs)

14

How is prostate cancer diagnosed?

- What is the most common stage?

- Transrectal US-guided prostate biopsy

- Histologic report: Gleason grading

- DRE >> clinical stage

  • Most common = T1c

- Risk stratification

Biopsy features + DRE = grade and stage then:

- Staging: imaging in intermediate/high risk

  • Bone scan and CT of abdomen/pelvis

15

Describe the staging of prostate cancer

- T1a, T1b by TURP

- T1c: non-palpable

- T2: palpable but organ confined

- T3a: extra-capsular

- T3b: SV invasion

- T4: invades adjacent organs

16

What is the median age of diagnosis of prostate cancer?

- Most common stage

- Peak when and why

- Median age of Dx: 66 yo

- Most in cT1c stage (localized): 60-75%

- Peak in 1992 due to PSA use

17

How are prostate cancer deaths changing?

Prostate cancer deaths are decreasing

- PSA finding cancer earlier

- Better treatments

18

What is the 5 year survival of prostate cancer:

- Localized

- Regional

- Distant

- All stages

Natural history of prostate cancer is very long:

- Localized: 100%

- Regional: 100%

- Distant: 28%

- All stages: 99%

19

What is management/treatment of prostate cancer?

Active surveillance

- Risk features

- Protocol for monitoring

Surgery

- Radical prostatectomy + bilateral pelvic LND

- Approaches and risks

Radiation

- External beam therapy

- Brachytherapy: radioactive seeds

Investigational

- Focal therapies

20

Describe TMN staging of organ-confined prostate cancer

Organ-confined: not though to involve regional LN or any visceral organs

- Clinical stage: cT1-3, N0, M0

21

Surgery is therapeutic and diagnostic for treating prostate cancer. What does it involve?

- Excision of prostate, seminal vesicles

- Excision of pelvic LNs

- Anastomosis of bladder to urethra

- Pathologic analysis > prognostic information

22

Describe TMN staging of advanced stage prostate cancer

- Locally advanced stage: cT4

- Nodal metastasis: N1

- Distant metastasis: M1

This scan shows something at femoral head (not kidneys, those normally light up), and actually has a lot of vertebral mets

23

What is treatment for advanced stage prostate cancer treatment?

Systemic treatment

- Androgen deprivation (ADT)

- Chemotherapy

- Other hormonal tx

Role for local therapy (Surgery, XRT) must be individualized

24

What are surgical and pharmacologic methods of androgen deprivation?

Surgical: orchiectomy

Pharmacologic:

- LHRH agonists: Lupron, Zoladex, Eligard

- Anti-androgens: Bicalutamide, Flutamide

- Older but occasionally utilized:

  • Ketoconazole
  • Diethylstilbesterol

25

SUMMARY of prostate cancer

- Screening

- Staging

- Treatment

Screening

- PSA and stage migration

- Long survival and low mortality make use of PSA controversial

Staging

- Overwhelming majority low-stage

- Most common stage

Treatment

- Risk stratified

26

Testis cancer is a ___ ___ tumor

Testis cancer is a germ cell tumor

27

What is seen here?

Testis cancer

28

Describe epidemiology of testis cancer:

- Most common malignancy in what population

- __% of all cancers in men worldwide

- Age of distribution is ____

- Ethnicity

- Most common malignancy in young men (15-34 yo)

- 1% of all cancers in men worldwide

- Age of distribution is bimodal

- Whites 5-6x more than blacks

29

What are risk factors for testis cancer?

- Undescended testicle (even if brought down)

- Maternal estrogen exposure

- Contralateral testis tumor

30

25% of men with testis cancer will present how? (important)

Subfertile semen parameters (in 25% of men with testis cancer)

31

What signs/symptoms contribute to diagnosis of testis cancer?

- Palpable mass

- Tender breasts (2%)

- Rarely with back pain

32

What is seen here?

- Left pic: irregular contour, heterogeneous echo

- Right pic: normal; homogeneous echogenecity, spherical/round

33

What are serum tumor markers that can help diagnose/monitor testis cancer?

Serum tumor markers:

- AFP

- beta-HCG

- LDH

Stage not defined fully until nadir of markers

34

How is the TNM stage of testis cancer established?

- Radical orchiectomy for T

- CT scan a/p for N/M

  • LNs of retroperitoneum! (due to vascular drainage; embryologically, testes start high and then descends. Only to inguinal LNs in late stages) 

35

Break down testis cancer staging for:

- Localized presentation

- Regional presentation

- Distant metastatic presentation

What are the 5 yr survival rates?

- Localized: 69% of cases

  • 5 yr survival: 99%

- Regional: 18% of cases

  • 5 yr survival: 96%

- Distant metastatic: 12% of cases

  • 74% 5 yr survival

36

What are the testis cancer types?

- What are products they make?

- What are most tumors

They are GERM CELL tumors

- Seminoma: 10-20%

  • Make B-hCG but never AFP

- Non-seminoma

  • Embryonal: 60% make AFP, 65% make B-hCG
  • Choriocarcinoma: ALL, 100%!, make B-hCG
  • Yolk sac: 90% make AFP
  • Teratoma

- Most are MIXED GCTs

37

What is the treatment for testis cancer?

- Treatment determined by stage + histology + risk category

- Surgery: orchiectomy (nearly always step 1)

- Observation

- Surgery: Retroperitoneal LND (RPLND)

- Chemotherapy

- Radiation therapy

38

Describe fertility preservation in testis cancer treatment

- Chemo is toxic to spermatogenesis

- RPLND can lead to retrograde ejaculation

  • Injury to ?

39

What are some newer concepts of long-term toxicities of testis cancer treatment?

- CV SE and metabolic synrome

- Pulmonary toxicity of bleomycin

- Secondary malignancy

  • Leukemia after chemo
  • Solid organ tumors after radiation

40

SUMMARY: Testis cancer

- Age

- Staging

- Young man's disease

- Staging

  • Primary tumor
  • Tumor markers (based on cell types present)
  • Imaging: to look at primary landing zone (retroperitoneal!)

41

Describe cancer of the male genitalia

Penile cancer: squamous cell cancer

42

What are risk factors for penile squamous cell cancer?

- HPV (positive in 30-60% of cases)

- Hygiene: circumcision

- Smoking

43

What is the incidence for penile squamous cancer?

.

44

How is carcinoma in situ managed? Prognosis?

- Topical treatment

- Can progress to invasive

45

Describe the staging and surgery for penile (squamous cell) cancer

Surgery:

- Partial penectomy

- Radical penectomy

- Inguinal LND

- Pelvic LND

46

Describe urothelial cancer

- Aka?

- Where can it occur

- Transitional cell carcinoma

Locations:

- Bladder

- Ureter

- Renal pelvis

47

What are risk factors for bladder cancer?

- Males (3x)

- Cigarette smoking ~ 50% of cases

- Occupational/environmental exposure: 20% of cases

  • Aromatic amines: plastics, chemical, rubber processing (and tobacco)
  • Aluminum, dye, pesticides, arsenic, leather processing, printing industry

- Infection

- Schistosoma hematobium

48

Describe the connection between bladder cancer and tobacco

- Smokers of > 2 packs/day have ~7x the risk of nonsmokers

- Risk in nonsmokers 1-2%

- Risk in smokers 6-10%

- Rationale for screening in firefighters

- Smoking cessation, even at time of diagnosis, improves bladder cancer survival

49

How is bladder cancer diagnosed?

Hematuria

- Gross painless hematuria >> automatic workup

- Microscopic hematuria >> more detail needed

Testing of microhematuria

- Urinalysis with micro (dip inadequate)

- Urine culture

- If >= 3 rbc/hpf in absence of infection -> workup

50

Describe the diagnostic workup of microhematuria in bladder cancer?

DDx:

- Kidneys: stone, mass, infection

- Ureters: stone, mass

- Bladder: stone, mass, infection

- Prostate: BPH

- Anticoagulation effect

- Trauma

- Prior pelvic radiation

- Atrophic vaginitis/urethritis

Prevalence of microhematuria: 1-20%

51

What are risk factors for hematuria?

- Age > 40 yo

- Male

- History of tobacco use

- Chemical exposure

- History of stones

- Symptoms

52

Workup for bladder cancer?

- CT abdomen/pelvis (3-phase)

- Cystoscopy

- +/- Urine cytology

53

What is the presentation of bladder cancer?

- Other symptoms (with microhematuria)

  • Dysuria
  • Urgency/frequenc
  • Burning or suprapubic pain

- Women frequently misdiagnosed and treated UTI even with gross hematuria

- 10% present with symptoms related to metastasis or advanced disease

  • Bone pain
  • Constitutional symptoms

54

How do you evaluate bladder cancer?

- Urine cytology

- Cystoscopy

  • Biopsy
  • Resection (TUR)
  • Bimanual exam

- Imaging

  • Hydronephrosis
  • Lymphadenopathy
  • Visceral lesions

55

Describe the staging of bladder cancer?

What is most common?

Stage [Tis -T4] + Grade [Low/High] 

56

Describe non-muscle invasive UC-bladder

- Stages

- Treatment

- Surveillance

- Management of recurrence

- Stages: Tis, Ta, T1

- Surgery: TUBT - Intravesical therapy:

  • Mitomycin
  • BCG: Bacillus Camille-Guerin

- Surveillance:

  • Regular interval cystoscopy
  • Annual imaging
  • Urine cytology

- Management of recurrence

- Depending on presentation, some chance of progression to more invasive disease

57

Describe muscle-invasive UC-bladder

- Stages

- Surgery

- Surveillance

- Management of recurrence

- Stages T2-T4

- Surgery:

  • Diagnostic TURBT + bimanual exam
  • Cystectomy/Cystoprostatectomy
    •  Radical cystectomy: women (bladder, +/- uterus, +/- anterior wall of vagina), man (bladder, prostate, seminal vesicles)
    • Bilateral pelvic LND

- Chemotherapy: neoadjuvant/ajuvant

  • CISPLATIN-based

- Chemoradiation

  • Non-surgical candidates
  • Inferior survival vs. surgery

- Urinary diversion:

  • Ileal conduit (incontinent stoma)
  • Neobladder (continent)
  • Continent cutaneous diversion

- Surveillance

  • Urine cytology
  • Scheduled imaging - Management of recurrence
  • Urothelial: upper tracts
  • Distant

58

What is shown here?

Urinary diversion

- Bowel segment with bowel re-anastomosis

59

Describe the pathology of bladder cancer (and percentages)

- Urothelial cell carcinoma (UC): 90%

- Squamous cell carcinoma (SCC): 7%

  • 85% of cases in Egypt secondary to Bilharzial infection (schistosomiasis)
  • Chronic irritation: long term catheter

- Adenocarcinoma: 2%

60

Describe urothelial cancer of the upper tracts

- Location

- Percnetages

- Ureter or renal pelvis

- 5-7% of all renal tumors

- 5% of urothelial cancers

  • > 80% of those had prior bladder cancer

61

Describe management/treatment for urothelial cancer in upper tracts

Surgery

- Endoscopy: biopsy and fulguration

- Resection: segmental, nephroureterectomy

Chemotherapy

62

Describe the survival of urothelial cancer

- Overall 77% alive and disease-free at 5 yrs

63

SUMMARY: Urothelial cancer

- Screening

- Staging

- Survival

- Bladder cancer is uncommon

Screening

- No routine or recommended screening

- Microhematuria!

- Target populations

Staging: bladder cancer:

- 80% are non-muscle-invasive at presentation

- 90% are urothelial (transitional) cell cancer

Survival

- Example of high cost of care

64

What is the most common kidney cancer?

Renal Cell Carcinoma

65

What are risk factors for kidney cancer (renal cell carcinoma)?

- Obesity

- Tobacco use

  • 20-40% of men with RCC
  • 10-20% of women

- Hypertension

66

Hereditary syndromes are responsible for __% of RCCs

Hereditary syndromes are responsible for 2-3% of RCCs

67

What are hereditary syndromes/causes of kidney cancer?

- Von Hippel-Lindau

- Tubeous sclerosis

- Hereditary papillary renal cell carcinoma

- Hereditary leiomyomatosis and RCC (HLRCC)

68

What is Von Hippel-Lindau syndrome?

- Inheritance pattern

- Locus

- Gene

- Cancer type

- Associated manifestations

- Age of onset

- Uni or bilateral

- Autosomal dominant

- Chr 3p

- VHL gene

- Clear cell renal cell carcinoma (in 50%)

- Associated manifestations: pheochromocytoma, retinal angiomas, hemangioblastomas of SC/brainstem, cysts of kidney/pancreas

- Early onset: 20s-40s

- Often bilateral, multiple

69

What renal cancer is associated with tuberous sclerosis?

- Clear cell renal cell carcinoma

- Also angiomyolipoma

70

What are the genetics/mechanism behind hereditary papillary renal cell carcinoma?

- Met proto-oncogene mutations

- chr 7q31-34

- Encodes hepatocyte GF

71

What cancers are associated with Hereditary Leiomyomatosis and RCC (HLRCC)?

- Genetics

- Cutaneous leiomyomas

- Uterine fibroids

- 20% have RCC

- Chr1q: fumarate hydratase gene

72

Describe the mechanisms for the following genes:

- VHL

- HIF

- VHL (TSG)

- VHL: codes for protein r/f degradation of HIF

- HIF: induces angiogenesis in hypoxic environment via regulation of VEGF/PDGF

- VHL (TSG) mutn: constitutive activation of HIF in normoxic conditions >> urnegulated angiogenesis

73

Describe the VEGF pathway and what gene is involved

VEGF pathway:

- Neovascularity, proliferation

- VHL: tumor suppressor gene

  •  Involved in VHL and sporadic RCC

Can target alteration with new meds

- Targeted therapy

74

What is the diagnostic workup for a renal mass?

- Imaging

  • Preferred: axial imaging (CT/MRI) pre and post-contrast phases
  • Alternative: renal US

- Urinalysis

- When considering malignancy in DDx:

  • Add chest x-ray
  • Labwork: renal function, CBC, livery function

75

What is the presentation of kidney cancer?

- Classic triad (TESTED)

- Gende

- Median age

- Syndromes

Classic triad (observed in under 25%)

- Hematuria: gross or microscpic

- Flank pain

- Palpable abdominal mass

Paraneoplastic syndromes common:

- Hypercalcemia

- Elevated LFTs

Epidemiology:

- Males (2x)

- Median age at dx = 64 yo

76

Describe the class of renal cystic lesions. How are they classified?

- Malignancy risk

Cystic lesions are classified on CT (Bosniak)

- Class I: simple cyst (0% malignancy risk)

- Class II: nonenhancing fine septum or Ca++ (minimal malignancy risk)

- Class IIf: hyperdense, multiple septa, wall nodules (5-15% malignancy risk)

- Class III: enhancing nodule or septa (50% malignancy risk)

- Class IV: enhancing soft tissue component (90% malignancy risk)

77

What is seen here?

Bosniak cysts

78

What has improved the incidental finding of kidney cancer and caused a stage migration?

CT era

79

Describe kidney cancer staging

- Stage I: confined to kidney, < 7 cm

- Stage II: confined to kidney, > 7 cm

- Stage III: outside capsule but within Gerota's fascia; can go to vena cava

- Stage IV: outside Gerota's fascia, to other organs, to LNs

80

What are some kidney cancer mimics?

25% of resected masses are benign

- Oncocytoma: along spectrum of chromophome

- Angiomyolipoma: characteristic macroscopic FAT on imaging

- Secondary malignancies: lymphoma, metastasis from other primary (breast)

81

What is done to treat kidney cancer?

- Active surveillance for small renal masses (

- Surgery

  • Nephron-sparing surgery: partial nephrectomy
  • Radical nephrectomy
  • +/- regional LN dissection
  • Mestastectomy in select cases

- Ablative therapies: cryotherapy, radiofrequency ablation

- Systemic therapy: "targeted" immunotherapy

- Molecular pathway modulators

  • VEGF inhibitors (anti-angiogenic): Bevacizumab (Avastin), Sunitinib (Sutent), SOrafenib, Pazopanib
  • mTOR inhibitors: GFs, Hif-1 regulation; Everolimus, Temsirolimus

- Cytokine therapy

  • Interferon, Interleukin-2
  • Much more toxic, only agent with any reported 'complete response'

82

SUMMARY: kidney cancer

- The small renal mass is most common

- Hereditary syndromes are rare

  • Think young, bilateral masses, other stigmata

- Treatment

  • Surgery is mainstay
  • Role for targeted therapy