11/20- Malignant Diseases of the GU system Flashcards
What is the most common urologic malignancies? Next?
- Prostate
- Bladder
- Kidney
- Testis
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)
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)
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)
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)
Describe family history role in prostate cancer/risks
- 2-3x increased risk of prostate cancer
- BRCA link: female relatives with breast/ovarian cancer
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
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
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
__% 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)
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
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%
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)
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
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
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
How are prostate cancer deaths changing?
Prostate cancer deaths are decreasing
- PSA finding cancer earlier
- Better treatments
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%
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
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
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
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
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
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
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
Testis cancer is a ___ ___ tumor
Testis cancer is a germ cell tumor
What is seen here?
Testis cancer
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
What are risk factors for testis cancer?
- Undescended testicle (even if brought down)
- Maternal estrogen exposure
- Contralateral testis tumor
25% of men with testis cancer will present how? (important)
Subfertile semen parameters (in 25% of men with testis cancer)
What signs/symptoms contribute to diagnosis of testis cancer?
- Palpable mass
- Tender breasts (2%)
- Rarely with back pain
What is seen here?
- Left pic: irregular contour, heterogeneous echo
- Right pic: normal; homogeneous echogenecity, spherical/round
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
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)
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
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
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
Describe fertility preservation in testis cancer treatment
- Chemo is toxic to spermatogenesis
- RPLND can lead to retrograde ejaculation
- Injury to ?
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
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!)
Describe cancer of the male genitalia
Penile cancer: squamous cell cancer
What are risk factors for penile squamous cell cancer?
- HPV (positive in 30-60% of cases)
- Hygiene: circumcision
- Smoking
What is the incidence for penile squamous cancer?
.< 1% in US
How is carcinoma in situ managed? Prognosis?
- Topical treatment
- Can progress to invasive
Describe the staging and surgery for penile (squamous cell) cancer
Surgery:
- Partial penectomy
- Radical penectomy
- Inguinal LND
- Pelvic LND
Describe urothelial cancer
- Aka?
- Where can it occur
- Transitional cell carcinoma
Locations:
- Bladder
- Ureter
- Renal pelvis
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
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
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
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%
What are risk factors for hematuria?
- Age > 40 yo
- Male
- History of tobacco use
- Chemical exposure
- History of stones
- Symptoms
Workup for bladder cancer?
- CT abdomen/pelvis (3-phase)
- Cystoscopy
- +/- Urine cytology
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
How do you evaluate bladder cancer?
- Urine cytology
- Cystoscopy
- Biopsy
- Resection (TUR)
- Bimanual exam
- Imaging
- Hydronephrosis
- Lymphadenopathy
- Visceral lesions
Describe the staging of bladder cancer?
What is most common?
Stage [Tis -T4] + Grade [Low/High]
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
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
What is shown here?
Urinary diversion
- Bowel segment with bowel re-anastomosis
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%
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
Describe management/treatment for urothelial cancer in upper tracts
Surgery
- Endoscopy: biopsy and fulguration
- Resection: segmental, nephroureterectomy
Chemotherapy
Describe the survival of urothelial cancer
- Overall 77% alive and disease-free at 5 yrs
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
What is the most common kidney cancer?
Renal Cell Carcinoma
What are risk factors for kidney cancer (renal cell carcinoma)?
- Obesity
- Tobacco use
- 20-40% of men with RCC
- 10-20% of women
- Hypertension
Hereditary syndromes are responsible for __% of RCCs
Hereditary syndromes are responsible for 2-3% of RCCs
What are hereditary syndromes/causes of kidney cancer?
- Von Hippel-Lindau
- Tubeous sclerosis
- Hereditary papillary renal cell carcinoma
- Hereditary leiomyomatosis and RCC (HLRCC)
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
What renal cancer is associated with tuberous sclerosis?
- Clear cell renal cell carcinoma
- Also angiomyolipoma
What are the genetics/mechanism behind hereditary papillary renal cell carcinoma?
- Met proto-oncogene mutations
- chr 7q31-34
- Encodes hepatocyte GF
What cancers are associated with Hereditary Leiomyomatosis and RCC (HLRCC)?
- Genetics
- Cutaneous leiomyomas
- Uterine fibroids
- 20% have RCC
- Chr1q: fumarate hydratase gene
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
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
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
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
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)
What is seen here?
Bosniak cysts
What has improved the incidental finding of kidney cancer and caused a stage migration?
CT era
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
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)
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’
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
