SM_235b: Urothelial Cancer Flashcards
Largest risk factor for urothelial carcinoma is ___
Largest risk factor for urothelial carcinoma is smoking
Describe molecular pathology of bladder cancer
Molecular pathology of bladder cancer
- Differences in detoxification pathways may influence bladder cancer risk
- Efficient elimination of toxins is protective
- N-acetyltransferase 2 (slow acetylators)
- Glutathione S-transferase M1 homozygous deletions
- Cytochrome P450 1A2 induction
- Papillary tumors: 9q, p15/16, p27
- CIS: p53, pRb, p14ARF, p21
____ pathway involving ____ has been implicated in low grade urothelial cancer
Proliferative pathway involving loss of 9q has been implicated in low grade urothelial cancer
____ pathway involving ____ has been implicated in high grade urothelial cancer
Dysplastic pathway involving p53 mutation has been implicated in high grade urothelial cancer
Describe molecular model of urothelial cancer progression
Urothelial cancer progression
- Normal urothelium (9p-/9p-)
- Hyperplasia -> superficial papillary low grade (FGFR3)
- Dysplasia (G1 > G2) -> carcinoma in situ
Describe signs and symptoms of urothelial carcinomas
Signs and symptoms of urothelial carcinomas
- Hematuria: 80%
- Irritative voiding symptoms: 20%
- Flank pain
- Palpable mass
- Mucosuria: adenocarcinoma
- Symptoms due to metastatic disease
Urothelial carcinoma involves ____
Urothelial carcinoma involves cystoscopy
- Trans-urethral resection of bladder tumor
- Urinary tract imaging
- Enhanced blue light cystoscopy
___ is by far the most common type of urothelial carcinoma
Transitional cell carcinoma is by far the most common type of urothelial carcinoma
- Bladder >> upper tracts > urethra
Prognosis of urothelial carcinoma ____ with increasing stage
Prognosis of urothelial carcinoma worsens with increasing stage
Most bladder cancer is ___ at diagnosis
Most bladder cancer is low stage at diagnosis
Recurrence risk for superficial bladder cancer increases with ____, ____, ____, and ____
Recurrence risk for superficial bladder cancer increases with stage, grade, multiplicity of tumors, and tumor size
Describe treatment of superficial bladder cancer
Superficial bladder cancer treatment
- Transurethral resection of bladder tumor (TURBT)
- Close surveillance
- Intravesical BCG
- Intravesical chemotherapy standard: MMC, thiotepa, doxorubicin, valrubicin
- Intravesical chenotherapy novel: gemcitabine, taxanes, and mitoxantrone
- Smoking cessation, greater intake of fruits and vegetables, decreased intake of fat and cholesterol, increased intake of non-chlorinated water
Describe natural history of T1 tumors
T1 tumors
- 25-30% progress to muscle invasion
- Frequently under-staged
- Often requires a second look transurethral resection of bladder tumor
Describe natural history of muscle-invasive bladder cancer
Muscle-invasive bladder cancer
- T2 and T3 tumors are endowed with the invasive phenotype de nova
- Radical cystectomy is treatment of choice
___ is treatment of choice for invasive bladder cancers
Radical cystectomy is treatment of choice for invasive bladder cancers
Neoadjuvant ___ is often used for invasive bladder cancer
Neoadjuvant chemotherapy is often used for invasive bladder cancer
- Improves survival
Invasive bladder cancer necessitates ____
Invasive bladder cancer necessitates retroperitoneal lymph node dissection
- Minimum dissection: bilateral external iliac, hypogastric, and obturator
- Extended dissection: pre-sacral and common iliac nodes
- Lymph node density is # of positive nodes divided by # nodes of removed
____ diversion is necessary after radical cystectomy for invasive bladder cancer
Urine diversion is necessary after radical cystectomy for invasive bladder cancer
- Non-continent: ileal conduit
- Continent diversion: neo-bladder, continent cutaneous diversion
Describe upper urinary tract urothelial carcinoma
Upper urinary tract urothelial carcinoma
- 50% develop bladder urothelial carcinoma
- 5% of bladder urothelial carcinomas develop upper urinary tract urothelial carcinoma
- Carcinoma in situ in bladder can recur in upper tracts
- Lynch syndrome: defect in DNA mismatch repair genes (MLH1, MSH2)
____ is a syndrome associated with urothelial carcinoma
Lynch syndrome is a syndrome associated with urothelial carcinoma
- Defect in DNA mismatch repair genes (MLH1, MSH2)
Upper tract urothelial carcinomas are treated with ____, ____, or ____
Upper tract urothelial carcinomas are treated with radical nephroureterectomy, segmental ureteral resection, and distal ureterectomy and reimplantation
Ureteral tumor may present as a ____
Ureteral tumor may present as a filling defect
Distal ureteral tumor is treated with ____
Distal ureteral tumor is treated with psoas-hitch ureteral reimplantation
Treatment of metastatic urothelial carcinoma is ____, ____, or ____
Treatment of metastatic urothelial carcinoma is
- MVAC: methotrexate, vinblastine, adriamycin, and cisplatin
- Gemcitabine + cisplatin
- PD-1 or PDL_1 inhibition
Describe segments of urethra
Urethra
Describe presentation of urethral cancer
Urethra cancer presentation
- Males: obstruction, hematuria, discharge, mass, fistula
- Females: bleeding, mass, obstruction
Most urethral cancer is ____ in males but is ____ in females
Most urethral cancer is proximal in males but is distal in females
- Urothelial is predominant histology for both
Describe anterior urethra cancer
Anterior urethra cancer
- Perform inguinal node dissection only if groin mass present
- Palpable nodes usually indicate metastatic disease
- Inguinal disease has been cured with node dissection
- Prophylactic node dissection has no proven clinical benefit
- Positive pelvic nodes is lethal disease
Posterior urethra cancer is managed with ____, ____, ____, and ____
Posterior urethra cancer is managed with radical cystectomy, prostatectomy, total urethrectomy, and penectomy
Anterior urethra cancer can invade ___ lymph nodes
Anterior urethra cancer can invade inguinal lymph nodes
Posterior urethra cancer can invade ___ lymph nodes
Posterior urethra cancer can invade pelvic lymph nodes
Anterior urethral cancer is ____, ____, ____, and ____ compared to posterior
Anterior urethral cancer is discovered earlier, lower stage at diagnosis, requires less radical resections, and has better overall prognosis compared to posterior
Stage T1 urothelial cancer involves ____ of bladder wall
Stage T1 urothelial cancer involves lamina propria of bladder wall
____ is associated with an increased risk of upper tract urothelial cancer
Lynch II syndrome is associated with an increased risk of upper tract urothelial cancer
Tumors involving the distal urethra are most likely to invade ____
Tumors involving the distal urethra are most likely to invade inguinal lymph nodes
