Urothelial and Renal Cancers Flashcards
1
Q
What is the epidemiology of urothelial carcinomas?
A
- arise within the “conduit system” and encompass tumors of the bladder ureters, and renal pelvis at a ratio of 50:3:1, respectively
- Patients with upper tract tumors (calyces, pelvis, ureters) have a 30-50% chance of developing bladder cancer in their lifetime
- Conversely, patients with a lower tract disease (bladder) have a 2-3% chance of developing upper tract tumors
- Annually about 60,240 new cases of urothelial cancer will be diagnosed in this country and it will account for 12,710 cancer-related deaths
- These tumors are more common in men than women (2-3:1); more common in Caucasians than in African-Americans (2:1); and have a peak incidence in the 7th decade
2
Q
What are risk factors for urothelial carcinomas?
A
- Acknowledged risk factors include:
- cigarette/marijuana smoking
- analgesic abuse (particularly phenacetin)
- urinary tract inflammation associated with a chronic infection (including S. hematobium)
- indwelling catheters
- stones
- occupational exposure to aryl amines
- Balkan nephropathy which predisposes to multifocal cancers of the renal pelvis and ureters
- patients with hereditary nonpolyposis colon cancer (HNPCC)
- prolonged cyclophosphamide/ifosfamide exposure
- Transitional cell carcinomas constitute about 90% of urothelial tract cancers and those exhibiting P53 mutations are particularly aggressive
3
Q
What is the presentation of urothelial cancers?
A
- Gross (total) hematuria is the most common symptom (75%). Irritative or “infection-like” symptoms are also common (30%)
- The latter classically are associated with carcinoma in situ
- Tumors involving the ureter or upper collecting system may present with flank pain or a palpable mass
- Some patients may also present with symptoms referable to locally advanced or metastatic disease
- These signs/symptoms will generally prompt CAT scans
- Such imaging studies might reveal a “filling defect” involving some component of the urothelial system which requires endoscopic evaluation of the lower tract (cystoscopy) or upper tract (ureterorenoscopy)
4
Q
What are histologic findings of urothelial carcinomas?
A
- Contingent on size and location, the tumor-bearing areas are either resected or sampled
- This is done in order to confirm a histologic diagnosis; determine whether the problem is unifocal or multifocal; and to assess the depth of invasion
- Urinary cytology may prove helpful in this assessment
- The general lack of sensitivity of urinary cytology to detect bladder cancer (particularly low grade tumors) has served as the impetus to identify more sensitive candidate markers in bladder cancer which can be identified in voided urine specimens, including
- human complement-H-factor (BTA STAT/TRAK tests)
- nuclear matrix protein (NMP) 22
- telomerase
- fibrin/fibrinogen degradation products (AuraTek FDP)
- tumor-associated hyaluronidase/hyaluronic acid
- nuclear shape/DNA content (Quanticyt)
- urothelium-associated cytokeratins (8,18,19,20)
5
Q
What is the management of superficial bladder cancers?
A
- Most bladder cancers are superficial which implies that they do not invade the true muscular wall of the bladder (tunica muscularis propria)
- Following resection, these tumors can be treated with topical therapy, usually intravesical BCG
- These patients require close surveillance with cystoscopy every 3 months for the first year; every 6 months during the second year; and yearly thereafter
-
Additional therapeutic adjuncts include
- providing the patient with help to stop smoking
- encouraging a liberal fluid intake to dilute the concentrations of carcinogens in the urine and stimulate frequent bladder emptying
- the use of antioxidant vitamin preparations (A, C, E, folic acid, B complex)
6
Q
What is the management of the upper tract urothelial cancers and muscle-invasive bladder cancer?
A
- Upper tract urothelial cancers and muscle-invasive bladder cancers will generally prompt more aggressive diagnostic testing to complete the staging workup (i.e. Chest x-ray and CAT scans of abdomen/pelvis) and to assess renal function (i.e. renal scan, creatinine clearance)
- Radical cystectomy (i.e. total removal of the bladder) is the “gold standard” treatment for muscle-invasive bladder cancer
- This also mandates the performance of an extended pelvic lymph node dissection and a urinary reconstruction (ileal conduit, continent urinary reservoir, or the construction of an orthotopic neobladder)
7
Q
What is the management of lower ureter urothelial carcinomas?
A
- Tumors of the lower ureter are best treated by distal ureterectomy and reimplantation of healthy ureter into a mobilized segment of bladder
- Tumors of the mid-ureter may be treated with resection and re-approximation of healthy tissue or nephroureterectomy
- Cancers involving the proximal ureter and upper collecting system are most often treated with radical nephroureterectomy (entire kidney and ureter, along with a portion of adjacent bladder wall), but endoscopic tumor ablation may be feasible in some cases
8
Q
What is the management of metastatic urothelial carcinomas?
A
- Urothelial cancers can metastasize to regional lymph nodes, lung, liver, bone, brain, and other sites
- For such patients, aggressive surgery is rarely beneficial and most patients are treated with platinum based chemotherapy (MVAC; cisplatin + Taxol; gemcitabine + cisplatin; carboplatin + Taxol)
- MVAC is an eponym for methotrexate, vinblastine, Adriamycin, and cisplatin. In general, the two-drug regimens are better tolerated than the four-drug MVAC regimen and appear to be equally effective
- Although overall response rates of 40-60% have been observed, most patients enjoy a median survival of only 12 months
9
Q
What is the epidemiology of renal cell carcinoma?
A
- Accounts for 2% of all cancers. In the USA, these tumors of the renal parenchyma are annually responsible for over 35,710 new cancer cases and 12,480 deaths
- This cancer occurs twice as often in men as in women. Most patients are >40 years old at diagnosis, with a predominance of patients in the 7th and 8th decades of life
- The incidence of RCCa has increased steadily
- In part, this may be a function of more frequent incidental detection of the tumor in patients who are subjected to ultrasound or CAT imaging (over 50% of currently identified cases)
10
Q
What are some risk factors for renal cell carcinoma?
A
- Postulated risk factors include
- cigarette smoking
- obesity, particularly in women
- hypertension/treatment for hypertension
- unopposed estrogen therapy
- exposure to petroleum products, heavy metals or asbestos
- acquired cystic disease associated with chronic renal insufficiency
- tuberous sclerosis.
11
Q
What are the familial diseases associated with renal cell carcinoma?
A
- Familial forms of the disease account for about 4% of all cases and are most often characterized by autosomal dominant inheritance
- young age at diagnosis (3rd-5th decades); and bilateral/multifocal tumors (exception—those involving papillary RCCa type 2)
- Some recognized hereditary variants include:
- von Hippel-Lindau disease [clear cell RCCa,3p25, impaired regulation of hypoxia inducible factor–HIF]; hereditary papillary carcinoma [papillary RCCa type 1, 7q31, MET proto-oncogene]
- hereditary leiomyomatosis renal cell cancer [papillary RCCa type 2, 1q42-43, fumarate hydratase]
- and the Birt-Hogg-Dube syndrome {hybrid oncocytic tumors, chromophobe RCCa, 17p11.2, BHD gene, fibrofolliculomas, colon polyps/tumors, pulmonary cysts, spontaneous pneumothorax]
12
Q
Briefly describe renal cysts and their classifications.
A
- The ultrasound and/or CAT scan features of these lesions permits their assignment to one of four categories, designated the Bosniak classification
- Type 1 lesions are uncomplicated benign cysts (1-3% malignancy rate)
- Type 2 cysts are minimally complicated but may include septations, minimal calcifications, infected cysts, and high-density cysts (10-20% malignancy rate)
- Type 3 lesions include multiloculated cysts, hemorrhagic cysts, complex septated cysts, lesions with dense calcifications, and multiloculated cystic nephromas (overall malignancy rate of 50%)
- Type 4 cysts are cystic renal cell carcinomas exhibiting irregular margins and solid/enhancing elements (100% malignancy rate)
- In general, type 1 and 2 cysts are observed
- Patients with type 3 and 4 cysts are advised to undergo surgery
13
Q
What are the indications for renal biopsy? What are potential complications?
A
- Renal biopsy is infrequently recommended
- Potential complications include:
- bleeding
- infection
- tumor dissemination (particularly with cystic RCCa)
- the potential that subsequent surgery may be rendered more difficult (especially nephron-sparing approaches)
- The recognized indications for renal biopsy include:
- to rule our lymphoma
- to exclude the possibility of a metastasis from a non-renal primary tumor
- to establish a tissue diagnosis in a patient with obvious metastatic RCCa before embarking upon non-surgical therapy
- to rule our cancer in a post-inflammatory pseudotumor.
14
Q
What is the clinical presentation of renal cell carcinoma?
A
- Currently, over 50% of the diagnoses are made after the detection of an incidental renal mass
- Other common presentations include hematuria (50-60%), abdominal pain (40%), and a palpable mass (30-40%)
- About 5% of patients will present with a broad range of paraneoplastic syndromes, such as hypercalcema, hepatic dysfunction, erythrocytosis and amyloidosis
- 1-3% of the tumors are bilateral
- Unfortunately, 25-30% of patients present with metastatic disease which most often involves the lung, bones, liver, and brain
15
Q
What is the management of renal cell carcinomas?
A
- A radical nephrectomy (open or laparoscopic) is the most common treatment for localized renal cancers
- Nephron-sparing surgery (partial nephrectomy) is a reasonable option for:
- patients with bilateral tumors
- cancers involving an anatomically or functionally solitary kidney
- for patients in whom the contralateral kidney is threatened by hypertension or diabetes mellitus
- for tumors ≤4cm (usually in the upper/lower pole) amenable to nephron-sparing surgery, even in the presence of a healthy contralateral kidney
- Small tumors may be amenable to cryoablation or radiofrequency ablation using minimally interventional techniques (CT-guided percutaneous approach vs. laparoscopy)
- Expectant management (“watchful waiting”) may be a reasonable option in elderly patients with significant medical comorbidities (especially for small, slowly growing, asymptomatic tumors)
