Pocket Oncology (Pocket Notebook Series), 1st Ed.

BLADDER CANCER

Helena A. Yu and Dean Bajorin

Epidemiology

• Most common malignancy of the urinary system, ∼74000 Pts will be diagnosed in the US in 2012, ∼15000 will die of their disease.

Etiology and Clinical Manifestations

• RFs: Smoking, aromatic amines, occupational exposures (metal, paint, rubber, leather, textile), HPV infxn, cyclophosphamide

• Presenting sx: Painless hematuria (typically intermittent & gross), irritative voiding sx (frequency, urgency, dysuria), flank or suprapubic pain (symptomatic of locally advanced disease), constitutional sx (fatigue, wt loss, failure to thrive) usually symptomatic of met disease

Workup and Staging

• Full eval of entire urinary tract: Cytoscopy, urine cytology (low Sn ∼34%, high Sp ∼98%) (Urology 2003;61:109), eval of upper tract by CT urogram, MRI, or IV pyelogram

• Initial cytoscopy includes bimanual exam to assess for locally adv disease, visual inspection of bladder, visible tumors biopsied or resected transurethrally, random biopsies if + urine cytology +no visible tumors

• UC are either low-grade or high-grade, w/muscle-invasive disease almost always high-grade

Prognosis

• Early stage prognostic factors: Stage, histologic grade, presence of multicentric disease, time to recurrence, tumor size, presence of CIS

• Met prognostic factors: Poor performance status, visceral mets

Management: Non-muscle Invasive Disease

• The majority (50–80%) of non-muscle invasive disease will recur if treated by TURBT alone, w/a proportion (20–25%) progressing to more invasive disease

• Low risk: Initial presentation w/non-muscle invasive Ta tumor, >1 y between recurrences, 3 or fewer lesions all less than 3 cm w/a papillary appearance, no T1 lesions, & no associated CIS, low-grade histology

• Tx of low-risk disease: TURBT alone ± 1 dose of intravesicular chemo (mitomycin)

• High risk: Multiple recurrences, more than 3 lesions or any >3 cm, T1, poorly differentiated, incomplete resection due to diffuse involvement or location, diffuse CIS, or CIS in a/w papillary lesions

• Tx of high-risk disease: TURBT, intravesicular tx (BCG, mitomycin) followed by restaging TURBT

• BCG: Unknown exact MOA, but triggers local immune response, given weekly × 6 wk, leads to fewer disease recurrences, consider maintenance Rx up to 1 y

• Surveillance: Cytoscopy & urine cytology 3 mos after initiation of BCG Rx

• Recurrent disease: Repeat intravesical tx, cystectomy should be considered for persistent disease after 1–2 cycles of intravesical Rx

• No recurrent disease: Repeat cystoscopy & urine cytology at 3–6 mos intervals for the 1st 4 y, then annually (Cancer 2002;94:2892)

Management: Muscle Invasive Disease

• Radical cystectomy is tx of choice for muscle invasive disease

• Neoadj cisplatin-based chemotherapy prior to cystectomy improves OS (Lancet 2003;361:1927)

• Regimens include MVAC or GC. Neoadj studies of MVAC resulted in ↑ pCR rate, non-significant ↑ OS w/significant tox. (NEJM 2003;349:859). GC = MVAC in met setting but ↓ tox w/GC, GC often used in neoadj setting

• No evidence for adjuvant chemotherapy after radical cystectomy

• Bladder preservation includes trimodality tx: TURBT, followed by concurrent chemoradiation (NEJM 2012;366:1477). Pt selection key, w/up to 40% requiring cystectomy for tx failure or disease recurrence. Criteria: Eligibility for complete TURBT, adequate renal function, UC histology, early stage (T2), no multifocal disease & no hydronephrosis

Management: Metastatic Disease

• Median survival w/met disease is 15 mos

• Cisplatin-based chemotherapy is the preferred initial Rx (MVAC, GC)

• GC preferred over MVAC due to equal efficacy w/less tox (less neutropenia, neutropenic sepsis, mucositis) (JCO; 2000:18:3068)

• If cisplatin ineligible (Cr clearance ≤60 mL/min or ECOG PS ≥2), use gemcitabine + carboplatin (JCO 2012;30:191)

• For nonplatinum regimen, suggest PG (paclitaxel + gemcitabine) (JCO 2001;19:3018)

• Single agents can be used but short response duration & no OS benefit

• 2nd-line options: Clinical trial preferred, pemetrexed (JCO 2006;24:3451), gemcitabine, ifosfamide, paclitaxel, vinflunine (in Europe)

Cancers of the Renal Pelvis and Ureter

• Upper tract disease tends to be multifocal (drop met), >90% are of urothelial origin, can be seen in Lynch syndrome

• Dx w/direct ureteroscopy & bx (brushings + urine cytology if no obvious 1°)

• Tx of localized disease is nephroureterectomy w/bladder cuff excision, no prospective evidence for (neo)adjuvant chemotherapy or radiation

• Tx of met disease is platinum-based (cisplatin or carboplatin) doublet chemotherapy

Molecular Biology and Targeted Therapy

• Initial studies targeting VEGF are promising: Bev (JCO 2011;29:1525)

• Initial studies w/multitargeted TK inhibitors are also promising: Pazopanib (Lancet Oncol 2012;13:810)

• FGFR-3 activating Mt found in >70% of low-grade superficial tumors, a/w favorable prognosis (J Pathol 2007; 213:91)

• PIK3CA alterations are found in up to 27% of heterogeneous tumor sets & are a/w lower grade & stage (Clin Cancer Res 2009;15:6008)

• TSC-1 alterations are found in 6–15% of bladder tumors & may be a/w response to mTOR inhibitors (Science 2012; 338:221)