Urothelial Carcinoma: Muscle-Invasive and Metastatic Disease
2018 July/August;13(4):23-36
References
What are the clinical features of bladder cancer?
Hematuria is the most common presentation of bladder cancer, although its specificity is far lower than traditionally thought. In fact, only about 2% to 20% of cases that present with hematuria are found to be caused by malignancy. However, the incidence of genitourinary tract malignancy is much higher in patients presenting with gross hematuria (10%–20%)8–10 than in patients with microscopic hematuria alone.8,10–14 Typically, hematuria associated with malignancy is painless. Multiple studies have shown, however, that hematuria can be a normal variant, with one study demonstrating that up to 61% of patients with hematuria had no identifiable abnormality.8,10,11,13
Abdominal pain, flank pain, dysuria, urinary frequency/urgency, or other irritative voiding symptoms in the absence of hematuria can be presenting symptoms of bladder cancer as well. In these settings, discomfort typically suggests more advanced malignancy with at least local involvement or obstruction. Suprapubic pain may herald invasion into perivesical tissues and nerves, while involvement of the obturator fossa, perirectal fat, urogenital diaphragm, or presacral nerves can often present with perineal or rectal pain. Similarly, lower abdominal pain may represent involvement of lymph nodes, and right upper quadrant pain may signal liver metastasis. Cough or shortness of breath may signify metastatic disease in the lung. Finally, back, rib, or other boney pain may suggest distant metastasis.
What next steps are required to complete this patient’s staging?
White light cystoscopy remains the gold standard for diagnosis and initial staging of bladder cancer. Additional tools include urine cytology and upper tract studies, including renal computed tomography (CT) urograms. Full urologic evaluation with all 3 modalities (cystourethroscopy, urinary cytology, and upper tract evaluation) is warranted for patients with a high suspicion for malignant etiology of hematuria. CT urograms are particularly useful for upper tract evaluation because they can be used to visualize kidney parenchyma, both renal pelvises and ureters, and pertinent abdominal and pelvic lymph nodes. Initial staging is completed through TURBT, which should ideally contain a segment of muscularis propria to distinguish between Ta (noninvasive), T1, and T2 tumors (Figure 1).
It is important to note, however, that traditional clinical staging approaches, including light cystoscopy and TURBT, have been known to understage tumors. One study demonstrated that more than 40% of clinical staging required upstaging after radical cystectomy.15 Any initial cystoscopy findings of either visible malignancy or suspicious lesion should be biopsied or fully resected transurethrally. If occult abnormality is absent in a patient found to have positive urine cytology, biopsy of normal-appearing urothelium is also indicated.
Regarding staging, T1 tumors are distinguished from Ta malignancies by their involvement in the urothelial basement membrane. Tumor invasion into the muscularis propria indicates T2 tumors, while T3 tumors extend through the muscle into the serosa and involve the complete thickness of the bladder wall. Involvement of nearby structures defines T4 bladder cancers, with T4a malignancies involving adjacent organs (prostate, vagina, uterus, or bowel) and T4b tumors involving the abdominal wall, pelvic wall, or other more distant organs. According to the American Joint Committee on Cancer’s most recent TNM staging system (Table 1),16 lymph node involvement in the true pelvis (that is, N1–N3) with T1 to T4a disease is now classified as stage III disease.
This differs from the 2010 recommendations, which classified any disease with lymph node involvement as stage IV disease. A tumor classified as either T4b or T1 to T4a with lymph node involvement beyond the common iliac nodes is now classified as stage IVA disease, and any distant organ involvement or lymph node involvement distal to the paraaortic lymph nodes now qualifies as stage IVB.
Bladder cancer is often broadly categorized as either non-muscle-invasive or muscle-invasive (which can include metastatic disease). This classification has important implications for treatment. As such, all diagnostic biopsies should be performed with the goal of reaching at least the depth of the muscularis propria in order to accurately detect potential muscularis invasion. If no muscle is detected in the initial specimen, re-resection is recommended if safe and feasible. In cases where muscle cannot be obtained, imaging evidence of T3 disease from CT or magnetic resonance imaging may be used as a surrogate indicator. Once muscle-invasive disease is confirmed, CT evaluation of the chest is also recommended, as bladder cancer can metastasize to the lungs; furthermore, patients are often at risk for secondary concomitant lung cancers given that smoking is the most prevalent risk factor for both. However, patients with small, indeterminate lung nodules not amenable to biopsy should not be denied curative intent treatment given the high likelihood that they represent benign findings.17
