11/20- Malignant Diseases of the GU system Flashcards
(82 cards)
1
Q
What is the most common urologic malignancies? Next?
A
- Prostate
- Bladder
- Kidney
- Testis
2
Q
Among men, ___ cancer is the most common.
This cancer is the #__ cause of cancer deaths in men
A
Among men, prostate cancer is the most common.
This cancer is the #2 cause of cancer deaths in men (2nd to lung)
3
Q
Bladder is the #__ most common and the #__ cause of cancer deaths (among men)
A
Bladder is the #4 most common and the #8 cause of cancer deaths (among men)
4
Q
T/F: There is no GU cancer in the top 10 causes of cancer in women. What is the highest?
A
- True; no GU cancer in top 10 women cancer cases
- Kidney cancer is #8 (only 3% of new cases)
5
Q
What are the risk factors for Prostate cancer?
- Which is most important
- What are modifiable risk factors
A
- 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
Q
Describe family history role in prostate cancer/risks
A
- 2-3x increased risk of prostate cancer
- BRCA link: female relatives with breast/ovarian cancer
7
Q
What is involved in prostate cancer screening?
A
- 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
Q
What is PSA? - What is it’s function? - Circulation
A
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
Q
Describe the expected values/diagnostic criteria levels of PSA
A
% 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
Q
__% of prostate cancer occurs in the ____ zone
A
75% of prostate cancer occurs in the posterior zone
- Habitus may make difficult; technical points
- PSA testing has caused “stage migration” (finding earlier)
11
Q
What has US Preventive Services Task Force (USPSTF) recommends what for prostate screening?
What does American Urological Association say?
A
- 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
Q
What is the sensitivity and specificity of PSA screening?
How to improve?
A
Overall
- Sensitivity: 35%
- Specificity: 63%
If stratify for PSA > 4:
- Sensitivity: 86%
- Specificity: 33%
13
Q
How should we manage screening of prostate cancer?
A
Need to focus on age-specific! recommendations and practices (and tx need to maximize cure and minimize ASEs)
14
Q
How is prostate cancer diagnosed?
- What is the most common stage?
A
- 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
Q
Describe the staging of prostate cancer
A
- T1a, T1b by TURP
- T1c: non-palpable
- T2: palpable but organ confined
- T3a: extra-capsular
- T3b: SV invasion
- T4: invades adjacent organs
16
Q
What is the median age of diagnosis of prostate cancer?
- Most common stage
- Peak when and why
A
- Median age of Dx: 66 yo
- Most in cT1c stage (localized): 60-75%
- Peak in 1992 due to PSA use
17
Q
How are prostate cancer deaths changing?
A
Prostate cancer deaths are decreasing
- PSA finding cancer earlier
- Better treatments
18
Q
What is the 5 year survival of prostate cancer:
- Localized
- Regional
- Distant
- All stages
A
Natural history of prostate cancer is very long:
- Localized: 100%
- Regional: 100%
- Distant: 28%
- All stages: 99%
19
Q
What is management/treatment of prostate cancer?
A
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
Q
Describe TMN staging of organ-confined prostate cancer
A
Organ-confined: not though to involve regional LN or any visceral organs
- Clinical stage: cT1-3, N0, M0
21
Q
Surgery is therapeutic and diagnostic for treating prostate cancer. What does it involve?
A
- Excision of prostate, seminal vesicles
- Excision of pelvic LNs
- Anastomosis of bladder to urethra
- Pathologic analysis > prognostic information
22
Q
Describe TMN staging of advanced stage prostate cancer
A
- 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
Q
What is treatment for advanced stage prostate cancer treatment?
A
Systemic treatment
- Androgen deprivation (ADT)
- Chemotherapy
- Other hormonal tx
Role for local therapy (Surgery, XRT) must be individualized
24
Q
What are surgical and pharmacologic methods of androgen deprivation?
A
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)
- **Chemo**therapy
- **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?
.\< 1% in US
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 (\< 4 cm)
- 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
