Chapter 090. Bladder and Renal Cell Carcinomas (Part 4)

Metastatic DiseaseThe primary goal of treatment for metastatic disease is to achieve complete remission with chemotherapy alone or with a combined-modality approach of chemotherapy followed by surgical resection of residual disease, as is done routinely for the treatment of germ cell tumors. One can define a goal in terms of cure or palliation on the basis of the probability of achieving a complete response to chemotherapy using prognostic factors, such as Karnofsky Performance Status (KPS) (...
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Chapter 090. Bladder and Renal Cell Carcinomas (Part 4) Chapter 090. Bladder and Renal Cell Carcinomas (Part 4) Metastatic Disease The primary goal of treatment for metastatic disease is to achieve completeremission with chemotherapy alone or with a combined-modality approach ofchemotherapy followed by surgical resection of residual disease, as is doneroutinely for the treatment of germ cell tumors. One can define a goal in terms ofcure or palliation on the basis of the probability of achieving a complete responseto chemotherapy using prognostic factors, such as Karnofsky Performance Status(KPS) (visceral disease or bone metastases rarely achieve long-term survival. Thetoxicities also vary as a function of risk, and treatment-related mortality rates areas high as 3–4% using some combinations in these poor-risk patient groups. Chemotherapy A number of chemotherapeutic drugs have shown activity as single agents;cisplatin, paclitaxel, and gemcitabine are considered most active. Standard therapyconsists of two-, three-, or four-drug combinations. Overall response rates of>50% have been reported using combinations such as methotrexate, vinblastine,doxorubicin, and cisplatin (M-VAC); cisplatin and paclitaxel (PT); gemcitabineand cisplatin (GC); or gemcitabine, paclitaxel, and cisplatin (GTC). M-VAC wasconsidered standard, but the toxicities of neutropenia and fever, mucositis,diminished renal and auditory function, and peripheral neuropathy led to thedevelopment of alternative regimens. At present, GC is used more commonly thanM-VAC, based on the results of a comparative trial of M-VAC versus GC thatshowed less neutropenia and fever, and less mucositis for the GC regimen.Anemia and thrombocytopenia were more common with GC. GTC is not moreeffective than GC. Chemotherapy has also been evaluated in the neoadjuvant and adjuvantsettings. In a randomized trial, patients receiving three cycles of neoadjuvant M-VAC followed by cystectomy had a significantly better median (6.2 years) and 5-year survival (57%) compared to cystectomy alone (median survival 3.8 years; 5-year survival 42%). Similar results were obtained in an international study of threecycles of cisplatin, methotrexate, and vinblastine (CMV) followed by eitherradical cystectomy or radiation therapy. The decision to administer adjuvanttherapy is based on the risk of recurrence after cystectomy. Indications foradjuvant chemotherapy include the presence of nodal disease, extravesical tumorextension, or vascular invasion in the resected specimen. Another study ofadjuvant therapy found that four cycles of CMV delayed recurrence, although aneffect on survival was less clear. Additional trials are studying taxane- andgemcitabine-based combinations. The management of bladder cancer is summarized in Table 90-2. Table 90-2 Management of Bladder Cancer Nature of Management ApproachLesion Superficial Endoscopic removal, usually with intravesical therapy Invasive Cystectomy ± systemic chemotherapy (before ordisease after surgery) Metastatic Curative or palliative chemotherapy (based ondisease prognostic factors) ± surgery Carcinoma of the Renal Pelvis and Ureter About 2500 cases of renal pelvis and ureter cancer occur each year; nearlyall are transitional cell carcinomas similar to bladder cancer in biology andappearance. This tumor is also associated with chronic phenacetin abuse and withBalkan nephropathy, a chronic interstitial nephritis endemic in Bulgaria, Greece,Bosnia-Herzegovina, and Romania. The most common symptom is painless gross hematuria, and the disease isusually detected on intravenous pyelogram during the workup for hematuria.Patterns of spread are like those in bladder cancer. For low-grade disease localizedto the renal pelvis and ureter, nephroureterectomy (including excision of the distalureter with a portion of the bladder) is associated with 5-year survival of 80–90%.More invasive or histologically poorly differentiated tumors are more likely torecur locally and to metastasize. Metastatic disease is treated with thechemotherapy used in bladder cancer, and the outcome is similar to that ofmetastatic transitional cell cancer of bladder origin.